Integrated physiology and pharmacology Flashcards
(283 cards)
1
Q
What percent weight of the cell membrane is lipid?
A
42%
2
Q
What percent weight of the cell membrane is protein?
A
55%
3
Q
What are the Na and K concentrations of the Extracellular fluid?
A
High Na concentration (100-140mM)
Low K concentration (5mM)
4
Q
What are the Na and K concentrations of the Extracellular fluid?
A
High Na concentration (100-140mM)
Low K concentration (5mM)
5
Q
Is the extracellular concentration of Ca high or low?
A
High
6
Q
Name 3 categories of transporters which lie in the membrane.
A
Carriers
Pumps
Channels
7
Q
What is the bicarbonate concentration outside the cell?
And what is its function?
A
25mM. Acts as a buffer.
8
Q
What is the name for a polymer comprising of 4 monomer units and give an example.
A
Tetramer. Na/K ATPase, comprised of 2 alpha and 2 beta subunits
9
Q
How does the Na/K ATPase pump maintain a low intracellular Na concentration?
A
By pumping out 3Na and taking in 2K
10
Q
Name two factors influencing passive transport.
A
Potential
Concentration
11
Q
How many genes are required to form the Na/K ATPase and why?
A
- The Na/K ATPase is a tetramer therefore it consists of 4 subunits. These are 2 alpha and 2 beta subunits. Different genes are required to form both.
12
Q
What is the turnover for carrier proteins?
A
10(2) to 10(3) per second.
13
Q
What is the name of a carrier that transports one molecule in one direction?
A
Uniporter
14
Q
What is the name of a carrier that transports two molecules in one direction?
A
Symporter (Cotransporter)
15
Q
What is the name of a carrier that transports two molecules in opposite directions?
A
Antiporter (exchanger)
16
Q
Why is the sodium potassium pump described as an electrgenic transporter?
A
Because when the pump moves out 3Na and in 2K there is a net movement of charge (there is an overall loss of 1 positive charge from the cell during every exchange.)
17
Q
Name an sodium potassium pump antagonist and describe how it works.
A
Digoxin. Digoxin binds to the enzyme in the extracellular part. This is the area that, when phosphorylated, binds to potassium. This can cause hyperkalemia as the extracellular K concentration increases as less is being taken into the cell.
18
Q
Why are channel proteins conductive?
A
There is a net movement of charge as ions pass from the extracellular matrix, through channel proteins, to the intraxellular matrix. This creates a current. Therefore, when open, channels are conductive whilst when closed, they’re non-conductive.
19
Q
What is the turnover for Channel proteins?
A
10(6) to 10(8) ions per second.
20
Q
Are channel proteins selective or non selective?
A
Both. They’re selective to Na, K, Ca and CL. They’re non-selective to everything else.
21
Q
Describe the cell membrane attached patch clamp technique.
A
This method is used to measure the electrical properties of a small portion of the cell membrane.
Initially a glass pipette with a very small opening ( roughly 1 micron) is used to make a very tight suction contact with a tiny part of the cell membrane. This contact is so tight that no ions are able to pass between the pipette and the membrane. The pipette initially contains a salt solution (ionic)
As a result, all of the ions which enter the piptte will be from a channel protein in the cell membrane. Thus, this tiny space will express a current. This current can be measured using an ultrasensitive electronic amplifier (Electrode) connected to the pipette.
22
Q
Who developed the patch and clamp technique? and when?
A
Nehr and Sakman in the 1980s
23
Q
Name a disadvantage to the cell-attached patch clamp technique.
A
The cell can rupture over time.
24
Q
Why is whole cell patch clamp better than cell attached?
A
Cell attached only provides a current recording for a select region of the cell membrane, this figure is then multiplied (x) to give a representation of the current expressed from every ion channel in the cell.
Whole cell however provides the current for the entire cell membrane, thus making it more accurate compared to cell attached.
25
In the equation I = N.P0.g.(Vm-Ei). What does the I represent?
Total current carried by population of channels.
26
In the equation I = N.P0.g.(Vm-Ei). What does the N represent?
Number of channels
27
In the equation I = N.P0.g.(Vm-Ei). What does the P0 represent?
Open probability. A P0 of 1 would mean that the channels are always open. The higher the P0 the higher the current.
28
In the equation I = N.P0.g.(Vm-Ei). What does the g represent?
Single cell conductance. This is the constant.
29
In the equation I = N.P0.g.(Vm-Ei). What does the Vm represent?
Membrane potential
30
In the equation I = N.P0.g.(Vm-Ei). What does the Ei represent?
Equilibrium potential ion i. This is the membrane potential and the ion potential. The bigger the driving force of ion movement, the bigger the current.
31
Name 3 types of chemical buffer in the body
Bicarbonate buffer
Phosphate buffer
Protein buffers.
32
What is a physiological buffer?
A physiological buffer is a system that controls a pH by controlling the body's output of acids, bases or CO2.
33
Give 2 examples physiological buffers.
Urinary system - this is the best system as it buffers the greatest quantity of acid however this can take several hours or days to occur.
Respiratory system - this can buffer much quicker than the Urinary system but it cannot alter the pH as much.
34
What is a chemical buffer?
A system that acts to minimise changes in pH by either accepting or donating protons.
A mixture formed of a weak acid and weak base
35
What two factors determine the amount of acid or Base that can be neutralised?
- the concentration of the buffer
| - the pH of their working environment
36
Name a weak acid
H2CO3
37
Name a strong acid
Hydrochloric acid (HCl)
38
Name a weak base
HCO3
39
Name a strong base
OH
40
What is a buffer power?
The amount of strong Base that must be added to a solution in order to raise the pH by a given amount.
Or
the amount of acid that must be added to a solution in order to lower the pH by a given amount.
41
How is fluroscene used in a technique to study intracellular pH?
Fluroscene is proportional to intracellular pH so that emission increases with pH..
As a result of this calibration is done at the end of the experiment to correspond certain emission intensities to their subsequent pH.
42
How are fluroscene pH measurements calibrated?
A proton iontophor is added to the cell, this allows the cell to become the same phone as the bath it's placed in. I.e if the bath is ph6 then the cell will become ph6. This allows us to calibrate the emission produced with the pH being analysed.
43
What 3 factors are involved in pH control?
Buffering, acid extrusion and acid loading.
44
How does acid extrusion occur and what proteins are involved?
Occurs at an Na/H exchanger antiport protein.
Under normal conditions Na is transported out of the cell whilst H is transported into the cell. Both are transported down their concentration gradients.
The Na concentration gradient is maintained by the Na/K ATPase
45
What is a setpoint I regards to acid extrusion?
A set point is essentially an on and off switch.
What the pH increases and the H concentration decreases below a certain set point the exchanger is off (so at alkaline pHs the exchanger is inactive)
So as the pH decreases (becomes more acidic), it switches on.
46
What is almost allomsteric modification of function in regards to the Na/H exchanger?
This is the process by which protons, other than the one being transported, bind to the exchanger. This leads to a conformational change in the structure of the protein which in turn increases it's activity.
47
Give 2 example of a protein involved in acid extrusion?
NHE1 found in the basolateral membrane and is involved in the regulation of pH and cell volume control.
NHE3 found in the apical membrane if the proximal tubule and is involved in bicarbonate reabsorption.
48
What drug inhibits NHE1 and how does it work?
NHE1 becomes inhibited by 'low' concentrations of Amiloride and it's analogue EIPA.
49
Give two clinical uses for amiloride.
Blocks Na/H antiport error proteins.
Used to act on the heart to minimise reaper fusion injury in ischemic attacks.
Used to block antiport proteins on the apical surfactant of proximal tubule cells in the nephron. This abolishes more than 80% of the action of angiotensin II on secretion of H in proximal tubule cells.
50
What is Enac?
Epithelial sodium channels which mediate sodium reabsorption in the aldosterone sensitive distal part of the nephron and collecting duct of the kidney.
51
What regulates Enac activity?
Aldosterone, angiotensin II, insulin and vasopressin.
52
How much alimoride is required to inhibit Enac?
50 micro Molar
53
How much alimoride is required to inhibit Na/K ATPase?
1 milli Molar.
54
How does acid loading occur and what proteins are involved involved?
Occurs as a result of Cl/HCO3 exchanger.
Under normal conditions the Cl moves into the cell whilst the HCO3 moves out of the cell.
Turns on in alkaline conditions and turns off in acidic conditions.
55
What family is the Cl/HCO3 antiport protein in?
Anion exchanger (AE) family.
56
When is there an exception in the function of the Cl/HCO3 antiport protein?
In red blood cells, during the hamburger effect whereby Cl is released and HCO3 is taken into the cell.
57
What are cardiac glycosides?
Organic compounds containing glycoside (sugar) that act on the contractile force of the heart.
58
Name 2 cardiac glycosides that inhibit the Na/K pump.
Digoxin
| Ouabain.
59
Give two factors involved in the tole of the Na/K pump.
Electrogenic transport of 3 +ve charges out of the cell and two +ve charges into the cell produces a net effect making the inside of the cell more negative.
More importantly the accumulation of K inside the cell establishes a greater and greater concentration gradient between that of the outside, thus increasing the driving force for K to leave the cell through K channel proteins - making the cell more negative.
60
Because the energy expenditure is so high to generate the concentration gradient produced from the Na/K pump, the movement of Na into cells is generally only through pathways with physiological significance - give two examples.
In the collecting duct of the nephron. Amiloride sensitive channels are on the apical membrane whereas the Na/K pump is known the basolateral. Rather than just recycling the Na this arrangement allows directional transport .
In excitable cells the Na entry produces decolonisation leading to the action potential being produced. The Na is recycled by the pump but an important physiological process is occurring.
61
Under normal conditions, what is the extracellular Ca concentration?
1mM (1000000nm)
62
Under normal conditions, what is the intracellular Ca concentration?
100nm
63
Why is Ca regulation important?
Can is an important second messenger involved in many signalling pathways.
64
Give an example of when Ca acts as a second messenger.
In pancreatic acinar cells. Acetylcholine, gastrin (CK-B) and substance Park Lloyd act as primary messengers which cause the release of cellular Ca. The Ca then acts as a secondary messenger to increase cyclic GMP and increase enzyme secretion.
65
The inward gradient of Na is 10 fold whilst the gradient for Ca is 10000 fold, how does the Na/Ca exchanger keep Ca concentrations low?
The exchanger is electrogenic in that it produces a slight change in the electrical potential of the cell. This occurs as a result of its stoichometry in that the exchanger brings in 3Na for every 1 Ca.
This causes the Na gradient to become magnified. The effect of the q0 fold gradient is cubed.
66
What gene family is the Na/Ca exchanger part of?
SLC8 family.
67
What super family is the SLC8 (Na/Ca exchanger) gene family part of?
CaCA superfamily.
68
What are the forms of Na/Ca exchangers called in mammals? (3 forms)
NCX1-3
69
What family are Ca ATPases and the Na/K ATPase part of?
P-type ATPase family
70
What 3 types of Ca ATPase do cells contain?
PMCA - Plasma membrane calcium pumps
SERCA
SPCA
71
What is a PMCA type calcium pump?
A plasma membrane calcium pump. This pump, alongside the Na/Ca pump, act to keep intracellular Ca concentrations low.
72
What are the SERCA type calcium pumps?
These are calcium pumps found on the sarcoplasmic or endoplasmic reticulum membranes.
73
What is the function of SERCA Ca pumps?
They reside in the sarcoplasmic reticulum of muscle cells. It is a Ca ATPase thatmoves calcium from the cytosol of the cell to the lumen of the sarcoplasmic reticulum during muscle relaxation. As this is an ATPase, ATP is hydrolyzed.
74
What are the SPCA type calcium pumps?
Ca pumps located on the Golgi apparatus.
75
What is the function of the SPCA type calcium pumps?
They supply the golgi apparatus with calcium (Ca) and Manganese (Mn) necessary for the production and processing of secretory proteins.
76
Give an example of when a SPCA calcium pump is used.
In the lactating mammary gland, SPCA seems to be the primary pump responsible for supplementing the milk with high (60-100mM) of calcium.
77
Name 4 types of plasma membrane pathways involved in Ca signalling.
VOCC - Voltage operated calcium channels
ROCC - Receptor operated calcium channels
MACC - Mechanically activated calcium channels
SORR - Store operated calcium channels.
78
Give an example of where voltage operated calcium channels (VOCC) are found.
In excitable cells. They're activated by depolarization.
79
Give an example of where receptor operated calcium channels (ROCC) are found.
In secretory cells and nerve terminals which are activated by the binding of an agonist.
Example. ndma receptors. A glutamate of glycine agonist binds to the receptor. This activates the channel and allows positively charged ions to pass through the membrane.
80
What are Mechanically activated calcium channels (MACC)?
Channels found in many cells which respond to cell deformation. These would include stretch mediated channel proteins.
81
What are store operated calcium channels (SOCC)?
Channels which are activated following the depletion of calcium stores.
82
Name the two classes of calcium channels in the store membranes.
IP3 receptors
| Ryanodine receptors.
83
Describe IP3 receptors.
A channel activated through the binding of IP3. This type of receptor is present on most cells types.
84
Describe Ryanodine receptors.
Low concentrations of ryanodine activate the receptor whilst high concentrations inhibit. Tends to be found in excitable cells.
85
What is the natural activator of ryanodine receptors?
cADP ribose.
86
What can stimulate ryanodine receptors other than the natrual activator cAMP ribose?
Caffine.
87
What is the name of the calcium current produced once SOCCs have been opened?
Calcium-release-activated-calcium current (ICRAC)
88
Name 2 proteins involved in re-establishing the lost calcium to the endoplasmic reticulum.
ORAI1 and STIM1
89
Name 3 potential mediators of ICRAC
- Phospholipase A2 Beta
- Nicotinic acid adenine dinucleotide (NAADP)
- STIM1 Protein
90
Why is it important to keep intracellular [Na] low in the epithelial cells of the thick ascending limb (loop of Henle)?
If intracellular [Na] was to increase then NaCl reabsorption is inhibited. The transepithelial osmotic gradient becomes dissipated resulting in diuresis and increased Na and Cl in the urine.
91
Define anatomical dead space.
The volume of the conducting airways.
92
What volume of air does anatomical dead space occupy?
Approximately 30% of inspired air (150ml)
93
Define physiological dead space.
The volume of the lungs that doesn't participate in gaseous exchange. This is equal to the conducting zone + non-functional areas of the respiratory zone.f
94
Define expiratory reserve volume.
The additional amount of air that can be expired from the lungs by determined effort after normal expiration.
95
Define residual volume.
The amount of air remaining in the lungs after fully exhaling.
96
What is FRC?
The sum of expiratory reserve volume and residual volume - approximately 2400ml in an 80kg average sized male.
97
What is pulmonary compliance?
A measure of the lung's ability to stretch and expand.
98
Give an example of a condition with a low lung compliance.
Pulmonary fibrosis. The paranchyma surrounding the lungs becomes more rigid, thus reducing the lungs ability to stretch and extend. Involves difficulty inspiring due to this.
99
Give an example of a condition with a high compliance.
Emphysema. Involves difficulty expiring due to the loss of elasticity of the lung tissue - reducing elastic recoil.
100
What happens when the volume is less than FRC?
There is a smaller volume in the lung so the forces favoring elastic collapse are low. The forces of the chest expansion are favored so the system expands.
101
What happens when the volume is higher than FRC?
The elastic forces in the lung favoring collapse are higher. The forces for chest expansion are now less favored (small) so the overall system collapses.
102
Give two clinical uses for Amiloride.
Amiloride blocks the H/Na exchanger which is part of acid extrusion. Amiloride is used to block these antiporters in heart muscle to minimise reprusion during ischemic attacks.
Also used to act on antiporters on the apical surface of proximal tubule cells in the nephron. Amiloride blocks 80% of Angiotensin II on the secretion of H, helping retain H
103
Give an example of an Na/H exchanger and describe its topography.
NEH1.
Has 12 transmembrane spanning domains.
Loop between 4-5 is linked to Na transportation
Loop between 6-7 linked to H extrusion.
Long intercellular C terminus with lots of potential binding regulatory sites.
Sensitive to calcium calmodulin which causes it activation.
104
What Na/H exchanger is found on the basolateral membrane and which is found on the apical?
NHE1 - basolateral
| NHE3 - Apical
105
How many subtypes of the Cl/HCO3 exchanger are there?
4 AE1-4
106
What inhibits the Cl/HCO3 exchanger?
DIDS - Stibene derivative drug.
107
What is the Cl/HCO3 exchangers role in RBCs?
AE1 is involved in complexes with Carbonic anhydrase and Aquaporin 1. They help optomise CO2 transport in the blood - hamburger shift.
108
What is the Equilibrium position in the lungs?
This is where the collapsing force of the lung is equal to the expanding force of the chest. Palv=Patm giving FRC
109
What happens when volume is less than FRC?
Lung forces are less than that of chest, favouring expansion. (happens as you breath out, leading to breathing back in)
110
What happens when volume is higher than FRC?
Lung forces are higher than that of the chest, favouring collapsig (happens progressively as you breath in, leading to breathing back out)
111
What happens to compliance as volume increases?
At low volumes, the lungs have a high compliance. At higher volumes however, the lungs have a lower compliance.
112
What 2 factors contribute to the elastic recoil of the lungs?
Anatomical component - Elastic nature of cells and extracellular matrix
Elastic recoil due to surface tension generated at air/fluid interface.
113
In an experiment with a cat lung, what happens in regards to changes in volume when the lungs are filled with fluid and when they're filled with air.
When filled with water (saline), very small pressure changes are required to increase the volume of the lungs.
When filled with air very little pressure causes very little changes in volume due to the surface tension at the air/fluid interface, once the pressure is high enough to overcome this tension, then the volume begins to increase.
114
What equation describes surface tension and what does it suggest would happen to alveoli? What is used to overcome this?
Laplace's equation (2T/r). Suggests that the air would move from an area of high pressure (small alveoli) to an area of low pressure (large alveoli) causing the smaller ones to collapse. Surfactant is produced (main constistuent is lipid) to overcome this problem.
115
How does surfactant compensate for the surface tension in the lungs? (rapidly expanding and slowly expanding)
The flow of surfactant slows the rate of inflation of the alveolar sacs, allowing the size of the alveolar sacs to be regulated.
If one is rapidly expanding, the surface density of the surfactant decreases, the surface tension and elastic recoil of the lipids therefore rise, putting a 'break' on expansion.
If one is slowly expanding, the surfactant is less diluted thus putting less 'break' on expansion.
This allows alveolar to be relatively the same size and helps limit the effects of surface tension, this increasing lung compliance.
116
What cells produce surfactant?
Type II Pneumocytes.
117
What is the main component of surfactant? And what percent does it make up?
DPPC (lipid) 35-40%
118
Suggest the clinical significance of surfactant.
Surfactant production decreases in pneumonia making the lungs harder to inflate (due to decreased compliance).
Surfactant isn't fully formed until 37 weeks gestation, may be a cause of premature birth.
119
The amount the surface tension is reduced by is proportional to what, regarding surfactant?
Number of lipids present in the surfactant.
120
What are the three types of air flow in the lung?
Laminar, tubrulent and transitional.
121
What is movement of air proportional to under laminar conditions?
Pressure gradient.
122
What is movement of air inversely proportional to under laminar conditions?
Resistance.
123
What is movement of air proportional to under turbulent conditions?
The square root of the pressure difference.
124
Why is turbulent flow favored over laminar in the early respiratory tract?
In laminar conditions, you need a much greater pressure gradient to get the same flow of air as a much lower pressure gradient under turbulent conditions. So, more effort is required for laminar than turbulent.
125
What is transitionaly air flow? Why does it occur?
The transition of laminar flow to turbulent and vice versa. Occurs in late respiratory tract due to an increase in cross sectional area, which come as a result of increased bifurcations in the bronchioles ect. In the straight portions, the flow is likely to be laminar whilst in the junctions its likely to be turbulent.
126
What number is used to determine what type of airflow is occuring?
Reynolds Number.
127
What is the equation for Reynolds number?
```
Re=2rvp/n
r=Radius
v=velocity
p=density of gas
n=viscosity
```
128
What does it mean if Re is less than (
The air flow is Laminar
129
What does it mean if Re is between 1000 and 1500 (under ideal conditions)
The air flow is transitional (both laminar and turbulent)
130
What does it mean if Re is greater than (>) 1500 (under ideal conditions)
The air flow is Turbulent
131
What is the Re number for laminar flow likely to be in physiological conditions?
Single figures.
132
What is used for determination of blood flow type
Reynolds number.
133
Why is turbulent flow majorly favored in the earlier respiratory tract?
Airways are not smooth tubes or surfaces.
Airways aren't even in diameter.
Laminar flow is proportional to pressure gradient, whereas, turbulent flow is proportional to square root of pressure difference to requires less effort.
134
What happens to the reynolds number with increased cross sectional area?
Decreases as the velocity of air decreases. This means the airflow transitions from turbulent to laminar.
135
What is Poiseville's law?
Airway resistance is proportional to gas viscosity and the length of the tube, however is inversely proportional to the fourth power of the radius.
Equation.
Resistance = 1/r(4)
136
Why would breathing be different for a deep sea diver?
They breath in helium along side oxygen. The gasses in the tank are denser than air so this will effect their airway resistance.
137
What are the impacts of Poiseville's law?
A very small change in airway diameter will have a large impact on resistance. A 10% decrease in airway diameter causes 50% more resistance.
138
What are the percentage contributions to airway resistance?
Airway resistance is greatest in the upper airways, which constitute 80%.
Parynx-larynx = 40%
Airways with a diameter >2mm = 40%
Airways with a diameter <2mm =20% (terminal airways)
139
What is the total airway resistance in someone with COPD (chronic obstructive pulmonary disease) compared to a normal healthy person?
In COPD there is an increased respiratory resistance due to inflamation in the terminal airways.
This produces a total airway resistance of around 5cm H20.s.litre-1
In a normal person this is1.5cm H20.s.litre-1.
140
Suggest two factors which impact airway resistance.
Mucus secretions - decrease diameter of airways.
| Oedema - Extra fluid in intersittial spaces of the lungs causes swelling and narrowing of airways.
141
What happens to the airways during inspiration and why does this occur?
There is a natural expansion of the airways (increased diameter to reduce resistance.).
This occurs because the alveolar pressure drops below that of atmospheric. This causes the transmural pressure of higher airways to increase as you move farther away from the lungs, thus increasing the diameter of higher airways. This provides smooth passage of airflow to the lungs.
142
What happens to the airways during expriation and why does this occur?
There is a natrual compression (collapsing) of airways.
This occurs because the alveolar pressure is now greater than that of the atmospheric pressure. As a result the transmural pressure in higher airways decreases the farther you go from the lungs. This causes the airways to collapse, decreasing their diameter and increasing resistance.
143
What is transmural pressure?
The pressure across the walls of the airways, it essentially is the pressure keeping the airways open.
144
Why do people with Emphysema natrually breath through pursed lips?
In emphysema, the elastic teathering which keeps the airways open deminishes as their main component (elastin) is broken down. As a result, less pressure is required to collapse the airways. To decrease the pressure to the lungs, they naturally decrease the diameter of their mouths, this decreases the pressure of the air flowing to the lungs, thus helping prevent the further collapsing of airways.
145
How does lung volume impact resistance?
When breathing in (inspiration) lung volume increases and total resistance decreases, this is because airways are opening up - increasing their diameter. The effects are the opposite for expiration.
146
Why are the effects of lung volume on resistance exaggerated in COPD?
They have a higher FRC, therefore the lungs are initially at a higher volume compared to that of a normal person, therefore resistance is higher at all volumes. This is due to the higher compliance of the lungs in COPD patients.
147
Why are the effects worse when respiratory rate increases in COPD patients compared to at rest?
At rest, the patient is still able to achieve close to complete tidal volume, however it takes longer. For example in a normal breath of 2.5 seconds, a healthy patient will achieve 100% filling of the lungs after 1 second. In a patient with COPD the lungs are only 60% full after 1 sec.
Increasing the respiratory rate will therefore drastically reduce the tidal volume of a COPD patient.
148
What type of protein cascades is the control of airway smooth muscle dependant upon?
GPCR - G protein coupled receptors.
149
What are the 3 G protein linked receptors associated with airway smooth muscle control?
Gq (contraction)
Gs (relaxation)
Gi (inhibits Gs pathway)
150
Describe the Gq pathway.
The Gq pathway is responsible for airway smooth muscle contraction.
The Alpha Gq protein is activated by an extracellular ligand agonist. The Alpha Gq protein subunit undergoes a conformational change whereby it associates, interacts and stimulates the activation of Phospholipsae C (PLC). PLC catalyses the hydrolysis of PIP2 producing IP3 and DAG (diacylglycerol). IP3 diffuses to receptors on SERCA channels located on calcium stores (SER and ER). This initiates the release of Calcium from these stores into the intracellular matrix. Calcium combines with calmodulin, forming calcium calmoduilin. This then activates Myosin light chain kinase which stimulates myosin in smooth muscle cells, thus instigating muscle contraction.
151
What receptors act in the Gq pathway?
M3 -Muscarinic receptors
H1 - histamine receptors
Bk - Bradykinin receptors
152
Describe the Gs pathway.
The Gs pathway is responsible for airway smooth muscle relaxation.
The Alpha Gs protein subunit is stimulated by an extracellular agonist (such as salbutamol) and undergoes a conformational change. This activates Adenylate cyclase which increases the intracellular Cyclic AMP concentration by catalysing the conversion of ATP to cAMP. cAMP acts as a secondary messenger causing the stimulation of BK potassium channels. These channels open causing potassium to move along its concentration gradient out of the cell thus inhibiting calcium influx.
cAMP also activates myosine light chain phosphotase which reverses contraction into relaxation whilst also inhibiting myosine light chain kinase.
153
What receptors act through the Gs coupled pathway?
B2 Adrenergic receptors.
154
What agonist works on B2 adrengergic receptors? what G protein coupled pathway is it associated with?
Salbutamol. Associates with the Alpha Gs coupled subunit. Leads to relaxation of airway smooth muscle.
155
What enzyme does the Gs coupled protein pathway initially activate? What does it catalyse?
Adenylate cyclase. Catalyses ATP to cAMP reaction
156
How many transmembrane domains do G proteins tend to have?
7
157
What is a G protein coupled receptor?
Proteins which detect ligands from outside the cell and activate internal transduction pathways ulitmately leading to a cellular response.
158
What is the function of the Gi protein pathway?
Inhibits the effects of the Gs pathway. So stimulation of the Gi pathway counteracts the stimulating effects of the Gs pathway, opposing relaxation of smooth muscle without instigating muscle contraction.
Also inhibits the BK potassium channel, so the Vm remains normal.
159
What receptors act through the Gi protein pathway?
M2 muscarinic receptors.
160
Give two humoral factors involved in parasympathetic and sympathetic pathways for smooth muscle.
Adrenaline - circulates around the body in the blood. Acts on B2 receptors thus instigating the Gs pathways, leading to muscle relaxation.
Histamine - released during inflammatory processes, acts on H1 receptors, initiating the Gq pathway, leading to muscle contraction.
161
Explain the role of M2 receptors in the parasympathetic pathway for airway smooth muscle.
M2 receptors are expressed on the post ganglionic terminal and are involved in the negative feedback of Ach.
Ach released from the post ganglionic terminal diffuses across the neuromuscular junction and initiates the Gq pathway in the smooth muscle cell, leading to contraction.
To prevent over stimulation of the muscle, some of the Ach released binds to M2 receptors on the post synpatic nerve which originally produced it, these M2 receptors then inhibit the further production of Ach, preventing overstimulation of the muscle.
162
What muscarinic receptor is primarily linked to muscle contraction?
M3
163
What receptors are involved in airway smooth muscle relaxation?
B2 adrenergic receptors (Gs pathway)
164
Name 2 a natural agonist for B2 adrenergic receptors, produced by the body and which one is stronger.
Adrenaline and noradrenaline. Adrenaline is stronger.
165
Name an agonist for B2 adrenergic receptors, used to treat the short term effects of asthma
Salbutamol.
166
Name two categories that can trigger asthma.
Atopic (extrinsic, allergens)
| Non-Atopic (intrinsic) cold air, drugs, respiratory infections.
167
What is the response to atopic and non-atopic triggers of asthma in asthmatic patients?
An inflammatory response is initiated. Inflammatory cells migrate to the airways were they release Histamine. Histamine binds to H1 receptors in the membrane of the smooth muscle cells lining the respiratory tract. This complex stimulates the Gq pathway, leading to bronchioconstriction.
168
What is FEV1 and why is it different for someone with asthma?
The amount of air you can forcefully breath out in one second. This is usually 100% in a normal person. In someone with asthma it's usually <80%. Their FVC (functional vital capacity) remains the same as they can fill their lungs but due to increased resistance from the constriction of the airways, its more difficult to expel the air.
169
What experiments have presented that a main cause of asthma is due to hyper-sensitivity and what did they show?
Antigen challenge, viral infections, ozone exposure and vitamin A deficiency.
All these experiments presented normal M1 and M3 receptors. However, there was a deficiency in neuronal M2 function. M2 are responsible for the Ach feedback loop. If these aren't working correctly, the relaease of Ach isn't inhibited, leading to over-stimulation of the smooth muscle. Resulting in bronchioconstriction.
170
What was the reason for M2 loss of function in the Antigen Challenge?
loss of M2 function came as a result of Eosinophils.
Eosinophils cluster around the nerve fibres and release Major Basic Protein (MBP).
MBP is an antagonist for M2 receptors thus preventing the negative feedback of Ach, leading to hypersentisivity and ultimately constriction.
171
Name an antagonist for M2 receptors.
Major Basic protein (MBP) produced by eosinophils.
172
Name along term agonist for B2 adenergic receptors in treating asthma
Salmeterol.
173
Why does Salmeterol have to be taken with corticosteroids?
Because it produces a background inflammatory response so the corticosteriods are supplied to reduce the inflammation.
174
Name an anticholinergic drug used to treat asthma and why it specifically is used.
Tiotropium bromide. This acts mainly on M1 and M3 muscarinic receptors which are found on the smooth muscle cell. It doesn't act on M2 receptors, allowing the feedback (although little) to occur.
175
Name a glucocorticoid used to treat asthma and briefly explain how it works.
Beclometasone. Used to change protein expression on a genomic level.
Activates the transcription of anti-inflammatory genes
Inhibits the transcription of inflammatory genes
Decreases the stability of some mRNA.
176
Why do glucocorticoids take a day or so to 'kick in'
They have to activate genomic effects,so this takes a while.
177
What can an asthmatic take if they're unable to take steroids?
Leukotriene modifiers. (theophylline also used.)
178
What brain group controls quiet inspiration?
Dorsal respiratory group
179
What brain group controls forced expiration?
Ventral respiratory group
180
What are the two centers of the pons which regulate rate and depth of breathing?
Pneumotaxic center and apneustic center
181
What is the function of the pneumotaxic center?
Increases the rate by shortening inspirations. Has an inhibitory effect on inspiration centers.
182
What is the function of the apneustic center?
Increases depth and reduces rate by prolonging inspiration. Stimulates inspiration center.
183
What is the Hering-Breuer reflex?
The process of stretch receptors in the lungs sending signals to the medulla to limit inspiration and prevent over inflation of the lungs.
184
What do centeral chemo receptors regulate?
Monitor conditions in the cerebro-spinal fluid sensing changes to Co2 concentration and Ph.
185
What do peripheral chemoreceptors regulate?
Located in the carotid artery and aortic arch, these chemo receptors respond to an increase in Co2, A decrease in pH and a decrease in O2.
186
What is the composition of air?
Dry and wet at standard atmospheric pressure of 760mmHg.
187
What is Dalton's law?
The total pressure of a mixture of gasses is the sum of their individual partial pressures.
188
What is Henry's law and what is it used to calculate?
[Gas]dis = S x Pgas.
s is solubility cooeficient (nits in mM/mmHg
P is partial pressure of gas.
Henry's law is used to calculate the amount of gas dissolved in a solution.
189
Describe Nitrogen Narcosis in deep sea divers.
Nitrogen has a higher solubility in lipid compared to blood, it acts like a volatile anesthetic and alters ion conductance.
As depth increases (30-90m) the concentration of dissolved Nitrogen in the blood increases.
190
What is decompression sickness?
A sickness which occurs from resurfacing too fast from deep water. Occurs because nitrogen comes out of the solution and forms bubbles.
191
Describe oxygen toxicity in deep sea divers.
```
Even at atmospheric pressure Hb is almost completely saturated with Oxygen, any excess dissolves into the plasma. Upon 40m depth, the oxygen partial pressure is equivelant to breathing 100% oxygen at sea level.
This is okay short term. Long term it can cause respiratory tract damage and CNS problems.
At 90m (10atm) it can cause seizures and comas.
```
192
Why is there an increased respiratory rate at high altitudes?
Minimises the difference between alveolar and ambient concentrations of Oxygen.
Loss of Co2 leads to Alkalosis which increases heart rate to provide Oxygen to tissues. Alkalosis is deminished through renal function
193
Define drug targets.
Non-receptor targets which produce a response.
194
Name 4 types of receptor families.
Ligand gated in channels
G protein coupled receptors
Kinase-linked receptors
Nuclear receptors
195
What governs the R to AR reaction?
Occupancy
196
What governs the AR to AR* reaction?
Efficacy
197
Define occupancy and give its equation
The proportion of receptors occupied will vary with the drug concentration.
Occupancy = Number of receptors occupied/total number of receptors.
198
What does an occupancy of 1 indicate?
All receptors are occupied
199
What does an occupancy of 0 indicate?
No receptors are occupied.
200
Define Emax
Efficacy is the relationship between receptor occupancy and the ability to initiate a response. The maximum response from an applied or dosed agent is the Emax.
201
Describe what technique is used to measure occupancy.
Radioligand biniding assays.
Uses a radioactive molecule ([H3] or [I125]) to measure the binding of a ligand to a protein.
Cells are prepared (may require use of detergent or centrifugation to separate membrane from cellular contents. Membrane is then separated onto filters.
Add radiolabel at different concentrations and equilibrate. After equilibrium remove unbound drug by filtration and count the radioactivity of the filter.
202
What factor decreases the validity of radioligand binding assays and how is it overcome?
Non-selective binding. This is the binding of the ligand to the tissue, not specifically to the receptor.
Measuring the proportion of specific and non-specific binding is essential to the assay. So to overcome this, the first experiment is conducted as normal. A second experiment is then conducted using lots of unlabelled (cold) lignad and radiolabelled ligand. The radiolabelled ligand cannot compete for occupancy so it's almost completely displaced from the recognition sites.
So all of the radioactivity produced will be from non-specific binding which is then deducted from the figures produced in the first experiment giving an estimate value for specific binding.
203
Which antiabsorbants can be used to reduce non sepcific binding?
Albumin or collagen for peptides
| O-catechol for catecholamines (noradrenaline, histamine ect - molecules made by nerve tissue)
204
Give 4 ways that radioligand degredation is overcome.
Using free radical scavenger (ethanol) in drug solution
Store at low temperature
Avoid light using dark bottles
Incorporation of antioxidants
205
Name an antioxidant used to prevent ligand degredation.
Ascorbic acid
206
Give 4 advantages and 2 disadvantages to using a [H3] radiolabel.
Advantages
- Indistinguishable from native compound
- Has high specific activities
- Stable when stored correctly
- Long half-life
Disadvantages
- Specialised labs are required
- Expensive and difficult to use
207
Give 2 advantages and 3 disadvantages to using [I125] as a radiolabel
Advantages
- Has aromatic hydroxyl group so it can be incorporated at very high specific activities
- Easy and cheap
Disadvantages
- Short half life (67 days)
- Biological activity can be reduced
- More readily degraded.
208
For tissue incubation, what does protein concentration need to range between and what should the assay volumes be?
Protein needs to be between 0.1 and 1mg
| Assay volumes need to be between 0.25 - 1ml
209
Name 2 types of additives used to protect ligands
Protease inhibitors are used to protect proteins
| Antioxidants such as ascorbic acid used if the ligand is oxidisable.
210
How is the seperation of solubilized receptors achieved. What is a major problem with this?
Cannot be achieved through filtration or centrifugation.
Achieved though,
- Dialysis
-Column chromatography
- Precipitation/adsorbtion
The rate of dissocation of ligand-receptor complex, is a problem. The speed of seperation must be compatible with the affinity of the ligand for the receptor (low affinity = High KD = faster/more efficient seperation.)
211
Define Bmax
The maximum amount of drug which can specifically bind to the receptors in one membrane portion.
212
Define Kd
Dissociation constant. The concentration of ligand which at equilibrium, occupies 50% of receptors. (a measure of affinity)
213
What does it mean if a drug has a low KD?
A low KD presents that at equilibrium only a small concentration of drug is required to occupy 50% of receptors, thus presenting that the ligand has a high affinity for the receptors.
214
What process is used for mRNA comparison?
RT-PCR
215
What process is used for protein comparison (seeing how many receptors are in a tissue)
Western blotting
216
Define EC50
An effective concentration giving 50% of the maximal response.
217
What is the receptor reserve?
Not 100% of receptors may be occupied to give a maximal response due to amplification signals. Some tissues can give a maximal response with <5% occupancy.
218
Define drug potency.
A measure of the response of a membrane in regards to the concentration of drug added.
219
Give an example of 2 highly potent and 2 less potent drugs.
Highly potent drugs evoke a given response at low concentrations (fentanyl or risperidone)
Loss potent drugs evoke the same response at higher concentrations (codine or diazepam)
220
Define efficacy.
A measure of a single agonist-receptor complex's ability to generate a response.
221
What is a partial agonist and how are they used clinically?
Partial agonists have a lower efficacy than their full agonist counterparts so they have the same EC50 but a different KD and maximum response.
They act as a competative antagonist to full agonists, eventually producing a decreased response.
Can be used to activate receptors to give a desired submaximal response when inadiquate amounts of endogenous ligand is present. So can reduce overstimulation of receptors when excess amount of endogenous ligand is present.
222
Give 3 examples of partial agonists
Buprenophine
Norclozopine
Buspirone
223
What 5 catagories of antagonism are there?
```
Chemical
Physiological
Pharmokinetic
Non-specific
Specific
```
224
Describe chemical antagonism, give an example.
The process by which substances combine in a solution so the effects of the active drug are lost.
Example - mercury poisoning.
Inactivation of heavy metals, tocicity is reduced by addition of Chelating agent such as dimercaprol
225
Name a chelating agent used to treat heavy metal poisoning.
Dimercaprol
226
Describe 2 versions of pharmokinetic antagonism, give an example
A reduction in the amount of drug absorbed.
Example - decreased abdorbtion from the GI tract produced by drugs which inhibit gut motility.
Opiates reduce absorption by oral route.
or
A change in drug metabolism
Patients treated with warfarin (anti coagulant used to thin blood to prevent heart attacks and stroke) must be careful when taking antibiotics such as penicillin as they can stimulate warfarin metabolism thus reducing its effective concentration in the blood.
227
Describe physiological antagonism, give an example
The interaction of two drugs with opposing actions in the body.
Example
Noradrenaline raises arterial blood pressure by acting on the heart and peripheral blood vessels. Whereas, histamine lowers arterial blood pressure by instigating vasodilation.
228
Describe non-competative antagonism
Don't block receptor directly, they block some steps in the process between receptor activation and response.
229
What is consecutive activity and what blocks it?
The ability of a receptor producing a response without being activated by a ligand interaction. These can be blocked by inverse agonists as they stabilise the resting state of a receptor.
230
What is the dose ratio?
How many more times agonist is required in the presence of an antagonist to establish the original submaximal response when no antagonist is present.
231
What is desensitisation?
Diminished responsiveness to stimulus
232
What is tachyphylaxis?
Diminishing response to successive doses of a drug rendering it less effective.
233
What are possible reasons for desensitisation and tachyphylaxis?
Loss of cell surface receptors
change in receptor configuration (phosphorylation)
Exhaustion of mediators
Increased metabolic degredation or extrusion of drug
Physiological adaptation.
234
Define PA2
The negative logarithm to the base 10 of the molecular concentration of an antagonist that makes it necessary to double the concentration of agonist to restore the original submaximal response when the antagonist is not present.
235
Suggest 5 factors influencing rate of drug absorption.
```
Site of administration
molecular weight
lipid solubility
pH and ionization
Carrier mediated transport
```
236
Why does pH and ionization effect drug absorption?
Many drugs are weak acid or bases. They're therefore effected by pH according to the Henderson-Hasselback equation. Weak acids or bases readily dissociate when a pH differs from their pKa making them become trapped in that location.
example - asprin has a pKa of 3.1. Renal tubules have pH of 7 meaning asprin becomes trapped due to its dissociation. Uninary aklalisation accelerated excretion whilst acidicifaction increases it.
237
Why does carrier mediated transport effect rate of abdsorption?
They're susceptible to saturation, denaturing and competition, thus limiting transport.
238
What is a 'pro drug'?
A drug which becomes active after it has been metabolised.
239
What allows electrical impulses to pass between adjacent cardiomyocytes?
Gap junctions between cardiomyocytes act as electrical synapses allowing the electrical current to flow between them.
240
What does Ohms law suggest in regards to electrical signals passing between two adjacent cells in the heart?
Ohms law suggests that the current flowing between cell A and its neighbouring cell B (Iab) is proportional to the voltage difference between them (Vab) but inversely proportional to the electrical resistance between them (Rab)
241
What is the main source of electrical resistance between neighbouring cardiomyocytes?
Gap junctions. The more compact the cells are the less the resistance from gap junctions as they're closer together, thus are minimal barriers to the flow of depolarizing current.
242
Why is initiation time, speed and duration of action potentials different in all parts of the heart?
This is distinctive for the 4 champers of the heart as they all have relatively different functions. These distinctions occur due to the cardiacmyocytes each region possesses.
These myocytes each posess their own unique composition of channel proteins and anatomy to cater for the function of their system. This allows various forms of action potential to be produced.
243
What are the 4 types of current in the heart myoctes?
Na current (Ina) - responsible for rapid depolarisation during action potential in atrial and ventricular muscle and in purkinje fibres.
Ca current (Ica) - responsible for rapid depolariation phase in SA and AV nodal cells, also triggers contraction in cardiomyocytes.
K current (Ik) - responsible for repolarisation phase of action potential in all cardiomyocytes.
Pacemaker current (If) - responsible for the pacemaker activity of SA and AV nodal cells and purkinje fibres.
244
What are the two electrogenic transporters in cardiomyocytes responsible for carrying current across the plasma membranes of cardiomyocytes?
NCX1 (H/Na exchanger)
| Na/K ATPase
245
What are the 2 fundimental principles of the SA node?
The inward depolerising currents interact with the outward repolarising currents to allow spontaneous depolarisation and repolarisation.
Currents interact within a narrow range of diastolic potentials (between -70 and -50Mv in SA and AV nodal cells whilst being between -90 and -65Mv in purkinje fibres).
246
Describe the generation of an Action potential in SA nodal cells.
Slow Na inflow brings the Vm towards -55mV threshold, Ica becomes increasingly active causing an influx of Ca thus raising Vm. Once depolarised K channels open repolarising the cell.
Depolarisation rapidly deactivates If and the process starts again
247
Where is the SA node located?
On the posterior region of the heart located in the wall of the right atrium at the junction of the superior vena cava.
248
Where does electrical conduction first disperse through once produced by the SA node? And what speed does it travel?
Conduction travels at 1m/s via arterial myocardium or bachmanns bundle in the left atrium.
249
Where is the AV node located?
Located on the posterior aspect of the heart just above the atrioventricular ring. located on the right side of the intraatrial septum near the ostium (opening) of the coronary sinus.
250
What are the 3 subzones of the AV node?
A, N, NV
A-N transitional zone (cells are smaller than arterial ones)
N zone (has round P cells similar to SA nodal cells)
N-H region - transitional zone near the bundle of his.
251
Where does the AV node delay occur (what subzone) and why does this delay happen?
Occurs in the A-N transitional region as conduction speed decreases to 0.05m/s delaying the impulse by 0.12 seconds allowing the atrial contraction to finish so the artia can empty their entire contents into the ventricles before the ventricles themselves contract.
252
Why are the heart muscle fibres in a spiral motion?
Spiral muscle contraction promotes tursion (twisting) which aids left ventricular ejection and untwisting aids relaxation and ventricular filling.
253
Describe an arterial muscle action potential.
Voltage gated Na channels open causing influx of Na, thus raising Vm. Influx of Na causes positive feedback cycle in that increased Na concentration stimulates Na channels to open, causing a rapid increase of Vm towards the nerst potential for Na.
Na channels close as cell depolarises (peak near +30mV)
Ca enters through slow channels prolonging depolarisation (so repolarisation doesnt happen too quickly) causing a plateau.
The plateau slowls decreases due to K channel leakage.
Ca channels close and K channels open causing a rapid K outflow returning the membrane to Vm (Na/K establishes normal Vm from hyperpolarised state.)
254
What is If regulated by? and what can alter this?
cAMP. B1 and B2 receptors increase cAMP (Gs) whilst M2 muscarinic receptors decrease cAMP.
255
What is excitation-contraction coupling?
The relationship between the electrical action potential and mechanical muscle contraction.
256
What is a benefit of electrical activity passing from cells to cell in the heart as oppose to chemical transmission?
Electrical conduction from cell to cell is much faster than chemical conduction at a synapse.
257
What structure (reminiscent of skeletal muscle) is responsible for the transmission of the action potential into the deep regions of cardiomyocytes? And how do they work?
T tubules. These are invaginations in the cell membrane which go down deep into the cell. This means that when an Action Potential passes through the membrane, it travels down these invaginations to the Sarcoplasmic Reticulum (and other Ca stores) quickly to rapidly instigate the release of Ca which is essential to muscle contraction.
258
What structure provide cell to cell connections for the transmission of an Action Potential between cells?
Intercalated discs present at gap junctions between cells. Allow action potentials to pass between neighboring cells allowing them to contract in unison.
259
What does the [Ca]i rise from and to during the plateau phase of a cardiomyocyte action potential?
100nm (10-9) to between 1-10 micromolar (10-6)
260
What is CICR?
Calcium induced calcium release. A rise in the intracellular [Ca] forms a positive feedback loops inducing the opening of more Ca ion channels, thus promoting the further influx of Ca.
261
What is the role of calcium in muscle contraction?
Calcium binds to troponin which is located on a troponin/tropomyosin complex the sarcomere. This induces a conformational change in the complex, displacing it and exposing the myosin binding site on the actin filament, this allows the binding of myosin to form crossbridges, which ultimately lead to muscle contraction (sliding filament)
262
Is actin thin or thick
| Is myosin thin or thick?
Myosin are thick
| Actin is thin
263
What is the tension in the cardiac muscle proportional to?
The number of cross bridges
264
What is the number of cross bridges proportional to?
The length of the sarcomere.
265
What ultimately determines the amount of tension produced by cardiac muscle?
The area of overlap in the sarcomere.
266
What is the optimum length of a sarcomere for maximum muscle tension to be achieved? what happens if they're shorter or longer than this?
2.2micro meters.
Shorter - there's a reduced number of cross bridges thus reducing tension (crossbridges fold so maximal overlap isnt occuring)
Longer - The area of overlap is less so fewer crossbridges occur resulting in less tension.
267
Define isometric in regards to muscle contraction.
No change in muscle length (in experiment, length is fixed but tension changes.) - carrying a box
268
Define isotonic in regards to muscle contraction.
No change in muscle tension ( in experiment, the tension is fixed but length changes) lifting a box.
269
What is resting tension?
The tension generated by the muscle without any stimulation.
270
What is the active tension?
The tension generated in the muscle when stimulated.
271
At what pressure is the optimum sarcomere length achieved in heart muscle cells? And what does this allow?
When the ventricles are filling (ventricular diastole) 10-12mm Hg. The filling of the ventricles sets the correct pressure for muscle tension and thus contraction. This allows maximal expulsion of blood into the arteries and into the pulmonary and systemic circulatory systems.
272
Why can heart muscle cells generate a wider range of tensions compared to skeletal muscle?
Skeletal muscle cells generate muscle tension through Skeletal Muscle Recruitment in that Motor Units (nerves innpvating specific numbers of muscle fibers) are recruited to increase muscle tension.
In the heart the muscle cells have an inbuilt ability to produce varied contraction allowing the heart to regulate it's degree of contraction.
273
What is the force velocity relationship?
Muscle force and contraction velocity are inversely related. (increased afterload increases pressure, contraction force therefore increases thus decreasing the speed that the muscle contracts.)
274
What is pre load and how does it effect heart muscle contraction?
Pre-load is the initial volume of blood in the heart chambers. This is the End Diastolic Volume in the ventricles. Increased Pre-load gives an increased Maximal Force (quicker contraction) due to increased pressure producing longer sarcomeres in muscle cells.
Pre-load of the ventricles maintains a pressure of 10-12mm Hg allowing sarcomere length to be at its optimum (2.2micrometers)
275
What is afterload?
The force the ventricles must contract to expel their contents, this is essentially arterial blood pressure.
276
What does a high afterload do to contractility?
An increased afterload decreases the speed of contraction as for a given afterload it's harder for the muscle to contract quickly.
277
What is Vmax?
The speed of contraction of the heart, this is a constant. Doesn't change with changes in pre-load.
278
What is P0?
Maximal force, the speed of contraction, this increases with increases in pre-load to an optimum.
279
Describe the role of preload in exercise.
During exercise, venous return increases so the blood volume in the ventricles increases (diastolic end volume) thus the preload increases, this increases the pressure and tension resulting in a faster heart beat. The pre load allows the heart to compete with an increased rate of contraction.
280
How does noradrenaline effect Vmas and maximal force?
Noradrenaline increases both Vmax and maximal force, thus increases heart rate and strength of contraction.
281
What is tachycardia?
Increased heart rate.
282
What is the intra-beat duration?
The time between action potentials.
283
Why does an increase in APs n the heart increase contractility? And what is the name of this process?
As the frequency of action potentials increases so does the tension until it reaches a maximum. This is due to the accumulation of calcium. This occurs because the cell hasn't established complete repolarisation allowing accumulation of Ca the more Aps that are fired, Ca is essential for muscle contraction and forming crosslinks. The more Ca, the more crosslinks, enhancing the strength of contraction.
