Health and Disease Flashcards
(402 cards)
1
Q
define pharmacology
A
the science of drugs and how they act in biological system
2
Q
What are the 4 main protein targets for drug action?
A
- receptors
- ion channels
- enzymes
- transporters
3
Q
What do ion channels do?
A
they are present on cellular membranes and open in response to environmental cues, which allows the passage of channel-specific ions down a concentration gradient
4
Q
What are the 2 ways in which drugs can affect ion channels?
A
blockers and modulators
5
Q
What do blockers do to ion channels?
A
they block ion channels and prevent ion movement
6
Q
What do modulators do to ion channels?
A
they don’t block the channel, but bind and increase or decrease the chance of the channel opening
7
Q
What are the 3 ways in which drugs affect enzyme activity?
A
inhibitors, false substrates, prodrugs
8
Q
How do inhibitors affect enzyme activity?
A
they block substrate from binding
9
Q
How do false substrates affect enzyme activity?
A
the enzymes produce an abnormal metabolite
10
Q
How do prodrugs affect enzyme activity?
A
drugs given to the patient are inactive, so enzymes convert them into active state
11
Q
What do transporters do?
A
transport substances across membranes, can be against a concentration gradient- but only ONE side of membrane is open at once
12
Q
What are the 2 ways in which drugs affect transporters?
A
inhibitors and false substrates
13
Q
How do inhibitors affect transporters?
A
they block activity of the transporter, so it can’t transport substances across the membrane
14
Q
How do false substrates affect transporters?
A
an abnormal compound will accumulate at the other side of the membrane
15
Q
What are receptors?
A
proteins that typically sit on cell membrane and respond to exogenous cues and relay a signal into a cell to produce a response
16
Q
What are the 3 ways in which a drug affects a receptor?
A
agonist, antagonist, modulator
17
Q
How do agonists affect receptors?
A
activates the receptor when it binds
18
Q
How do antagonists affect receptors?
A
bind to receptor, but produce NO response, and block activity of the receptor by endogenous activators
19
Q
How do modulators affect receptors?
A
they bind to elsewhere on the receptor and increase or decrease the ability of the receptor to activate
20
Q
define receptor
A
proteins, usually on the surface of a cell which receive and transduce signals
21
Q
define ligand
A
something that binds, can be an agonist or antagonist
22
Q
define agonist
A
something that binds and produces a response
23
Q
define antagonist
A
something that binds and produces NO response
24
Q
define second messenger
A
a molecule that relays a signal from a receptor to an effector
25
define signal transduction
a sequence of second messengers that elicit a biological response
26
How do receptors work?
1. ligand binds to receptor
2. causes a conformational change of the receptor protein
3. results in a cellular effect
27
What are examples of cellular effects after a receptor is activated?
opening of a channel, activation of a linked enzymes. recruitment of an effector protein, intracellular transport
28
What are the 4 main families of receptor?
1. ligand-gated ion channels
2. G protein-coupled receptors
3. Kinase-linked receptors
4. nuclear receptors
29
How do ligand gated ion channels work?
when a ligand binds, it opens the channel, allowing the movement of channel-specific ions
30
What is an example of a ligand gated ion channel?
acetylcholine and nicotonic receptors
31
How do acetylcholine and nicotonic receptors work?
1. an electrical impulse travels down the pre-synaptic neurone
2. this triggers the release of acetylcholine
3. acetylcholine acts on nicotinic acetylcholine receptors on the post-synaptic neurone
4. this opens the channel, and allows sodium ion entry, which triggers an impulse in the next neurone
32
What is kinase?
a second messenger and an enzyme
33
What does kinase do?
it uses ATP to phosphorylate targets, and acts as a switch to turn target on or off and allows other 2nd messengers to bind to phosphorylated target protein
34
How do kinase-linked receptors work?
1. the receptors is on the cell membrane as two halves
2. when ligand binds to receptors it brings the two receptors halves into a dimer
3. activates kinase activity of the receptors and a cascade and biological response
35
What is an example of a kinase-linked receptor?
epidermal growth factor receptor
36
How is epidermal growth factor receptor (EGFR) related to lung cancer?
EGFR can promote cell growth, and some patients with lung cancer may express many more EGFR receptors, so experience more growth
37
What is a G protein-coupled receptor?
a receptor with 7 transmembrane domains coupled to a G protein
38
How do G protein-coupled receptors work?
ligand binding activates the G protein bound on the intracellular surface, which interacts with an affector
39
How are G protein-coupled receptors activated?
1. receptor is in resting state attached to G protein
2. ligand binds and G protein is activated
3. GDP is exchange for GTP by G protein
4. GTP bound G protein interacts with the target effector, which causes a response
5. the G protein then hydrolyses GTP to GDP and the G protein can dissociate from the effector
40
What is an example of a G protein-coupled receptor?
muscarinic receptors and smooth muscle contraction
41
How do muscarinic receptors work?
1. muscarinic M3 G-protein coupled receptors are on intestinal smooth muscle
2. acetylcholine activates M3 receptors
3. the G protein is then able to bind to effector
4. contraction of smooth muscle occurs
5. therefore, antimuscarinics can be used to treat IBS
42
How do nuclear receptors work?
1. the receptor is NOT associated with the cell membrane, but in the cyotplasm
2. ligand enters the cell and binds to receptor in the cytoplasm
3. ligand-receptor pair allows it to change conformation and it can move into nucleus
4. it then binds to DNA and acts on gene expression
43
What is an example of a nuclear receptor?
oestrogen receptor
44
How are oestrogen receptors associated with breast cancer?
some patients with breast cancer may have more oestrogen receptors, so there is more growth
these receptors can be targeted by Tamoxifen
45
What is blood production controlled by?
multiple protein cytokines (release by WB cells) and growth factors
46
What detects blood vessel damage?
platelet surface receptors
47
What do platelets secrete? Why?
soluble factors to activate neighbouring platelets
48
What is required for a clotting cascade?
multiple blood proteins
49
What does thrombopoietin do?
regulate production of platelets
50
What does erythropoietin do?
regulate production of erythrocytes
51
What are the major precursors of platelets?
megakaryocytes
52
What kind of cells give rise to haematopoietic precursors of blood cells?
pluripotent stem cells
53
What creates a bruise?
when blood vessel endotheliums become damaged and blood leaks into surrouding tissues
54
What is the scientific name for blood clotting?
haemostasis
55
What 2 stages can clotting be broken down into?
1. primary haemostasis
2. secondary haemostasis
56
What happens in primary haemostasis?
platelets form a plug and are attracted to site of damage
57
What happens in secondary haemostasis?
a blood clotting mechanism is used to transform and stabilise the weak platelet plug into a clot by a fibrin network
58
What is the 1st step of platelet plug formation?
adhesion
59
What are the steps of adhesion in platelet plug formation?
1. damage to endothelium cells exposes subendothelial tissue which is made up of collagen fibres
2. collagen activates platelets and they adhere to these collagen fibres via an intermediate protein called von Willebrand factor (vWF)
3. platelets binding to collagen causes a release of ADP and serotonin from their secretory vesicles, resulting in more platelet activation
60
What is the 2nd step of platelet plug formation?
platelet activation
61
What are the steps of platelet activation?
1. release of ADP and serotonin from vesicles
2. this causes change in shape and surface protein expression of platelets
62
What is the 3rd step of platelet plug formation?
platelet aggregation
63
What are the steps of platelet aggregation?
1. platelets adhere to each other to form a plug
2. synthesis and release of thromboxane A2 from arachidonic acid enhances more activation and aggregation
64
What stabilises the platelet plug?
fibrinogen bridges that form when receptors in the platelet surface become exposed during activation
65
What causes contraction of the plug?
actin and myosin
66
What do healthy endothelial cells do?
synthesis and release of Prostacyclin (PGI2) and nitric oxide, which both inhibit platelet activation
67
What is the scientific name for a clot?
a thrombus
68
What is a clot?
the transformation of blood into a gel consisting of fibrin polymers that occurs around the platelet plug
69
What does vessel damage activate?
a cascade of enzyme that results in the activation of an enzyme called thrombin
70
What does the enzyme thrombin do?
cleaves a protein called fibrinogen into fibrin molecules that create the fibrin network
71
Sequence of events
clotting factors -> prothrombin -> thrombin -> fibrinogen -> fibrin -> blood clot
72
What are the overall steps of blood clotting?
1. damage to blood vessel lining triggers the release of clotting factors
2. formation of the platelet plug and vasoconstriction limits blood flow
3. development of the clot and fibrin strands adhere to form an insoluble clot
73
How is thrombin activated?
activated from prothrombin which then cleaves fibrinogen to fibrin (which is stabilised by activation of factor 8 by thrombin)
74
What are the steps in activating the clotting cascade for the extrinsic pathway?
1. initiated by a tissue factor, not blood protein, on the outside of plasma membrane of cells in the sub-endothelial tissue
2. tissue factors activates factor 7 and they both activate factor 10
3. generates small amounts of thrombin
4. thrombin then feeds back onto the intrinsic pathway to activate components and generate more thrombin
75
What are the steps of beginning the enzyme cascade in the intrinsic pathway of the clotting cascade?
1. clotting factor 12 is activated by contact with collagen
76
What is the role of the liver in blood clotting?
- produces many clotting factors
- produces bile salts which are required for absorption of vitamin K needed for production of prothrombin
77
What does thrombin do?
it is an enzyme that recruits the intrinsic pathway and activates factor 5 and activates platelets
78
How does the protease activated receptor on platelets activate them?
1. the enzyme thrombin binds and cleaves the thrombin receptor at a specific site on the N terminus on a platelet
2. the cleaved N terminus can then bind and activate the receptor on the platelet
79
What are examples of clotting disorders?
damage to endothelium (myocardial infarction), clots (deep vein thrombosis), clotting disorders (haemophilia)
80
define pharmacology
the science of drugs and how they act in biological systems
81
What are the 4 main protein targets for drugs?
1. receptors
2. ion channels
3. enzymes
4. transporters
82
Which 2 ways do drugs affect ion channels?
blockers, modulators
83
How do blockers affect ion channels?
they block ion channels and prevent ion movement, paticularly VGNC
84
How do modulators affect ion channels?
they don't block but they regulate how easily the channel opens or closes, and may need a lower or higher voltage -> so increase or decrease the chance of the channel opening
85
Which 3 ways do drugs affect enzymes?
1. inhibitors
2. false substrates
3. prodrugs
86
How do inhibitors affect enzyme activity?
they block activity by binding to active site
87
How do false substrates affect enzymes?
they bind to the enzyme and produce an abnormal metabolite
88
How do prodrugs affect enzymes?
they are drugs in an inactive state and bind to enzymes to be activated
89
Which two ways do drugs affect transporters?
inhibitors and false substrates
90
How do inhibitors affect transporters?
blocks activity of the transporter so it can't move substances across the membrane
91
How do false substrates affect transporters?
transporter thinks it is a different substrate, so an abnormal compound accumulates
92
What are the 3 ways in which drugs can affect a receptor?
agonist, antagonist, modulator
93
How do agonists affect receptors?
they bind to and activate the receptor
94
How do antagonists affect receptors?
they bind to the receptor and block activity by other activators -> do NOT activate it though
95
How do modulators affect receptors?
they bind elsewhere on the receptor and increase or decrease the ability of the receptor to activate
96
define receptor
proteins, usually on the surface of a cell which receive and transduce signals
97
define ligand
something that binds
98
define agonist
something that binds and induces a response
99
define antagonist
something that binds and produces NO response
100
define second messenger
a relay signal from a receptor to effector
101
define signal transduction
a sequence of second messengers that elicit a biological response
102
What are the steps of a basic ligand-receptor interaction?
1. ligand binds to receptor
2. this causes a conformational change of the receptor protein
3. this results in a cellular effect e.g. opening of a channel
103
What are the 4 main types of receptor?
1. ligand-gated ion channels
2. G protein-coupled receptors
3. kinase-linked receptors
4. nuclear receptors
104
How do ligand-gated ion channels work?
substance binds to it and opens the channel, allowing movement of channel-specific ions
105
What is an example of a ligand-gated ion channel?
acetylcholine and nicotinic receptors
106
What is the function of kinase?
an enzyme and second messenger that uses ATP to add a phosphate to targets, activating them
107
How do kinase-linked receptors work?
the receptor is on the cell membrane as two halves and binding bring them together, which activates kinase activity and causes a cascade
108
What is an example of a kinase-linked receptor?
epidermal growth factor receptor and lung cancer -> EGFR promotes cell growth, so patients with more of these proteins experience mroe growth
109
How do G protein-coupled receptors work?
they are receptors with 7 transmembrane domains coupled to a g protein and ligand binding activates the G protein which interacts with an effector
110
What is an example of G protein-coupled receptors?
muscarinic receptors and smooth muscle contraction
111
How do nuclear receptors work?
the receptor is NOT on the cell membrane, but in the cytoplasm -> ligand-receptor pair allows it to change conformation and it can move into nucleus where it binds to DNA and acts on gene expression
112
What is an example of nuclear receptors?
oestrogen receptor and breast cancer
113
Which 2 factors determine a receptor response?
affinity and efficacy
114
define affinity
how well a drug binds to a receptor
115
define efficacy
how well a drug activates a receptor
116
How are receptor responses measured?
concentration-response curves
117
How are concentration-response curves plotted?
a chosen response is recorded e.g muscle contraction and the recorded response is plotted against LOG agonist concentration
118
describe and explain the concentration-response curve
1. initial low concentration gives limited response as low receptor binding
2. more agonist is added and there is more binding
3. a plateau is reached as we either have full receptor occupancy or we have added all agonist and can't get a higher biological response
119
define Emax
the maximum response produced by an agonist
120
define EC50
the concentration of agonist needed to give 50% of Emax
121
How can we compare agonist drugs in the same biological system?
compare the profile of their concentration-response curves, Emax and EC50 values
122
What does it mean if another agonist has a curve to the right?
it has a higher EC50, so a higher concentration of agonist is needed to give the same response, so the agonist is LESS POTENT that the other
123
What do different EC50 values indicate?
different potencies for the receptor
124
define partial agonist
an agonist that binds to a receptor but does not produce a FULL response - either poor efficacy or affinity
125
What does the concentration-response curve look like for a partial agonist?
it will have an Emax below a full agonist and different EC50
126
define inverse agonist
an agonist that reduces a biological response below basal levels
127
What does the concentration response-curve look like for an inverse agonist?
Emax is below basal level
128
What is an example of an inverse agonist drug?
drugs that reduce heart muscle contraction -> heart has basal level of activity without any agonist present
129
define biased agonism
when different agonists bind to the same effector but activate different second messengers and create a different reponse
130
What is an example of biased agonism?
G protein-coupled receptors can signal through a G protein or arrestin
131
define arrestin
proteins that regulate the signalling of G protein-coupled receptors
132
define balanced agonist
an agonist that activates both pathways to the same level
133
What are the 2 types of competitive antagonist?
reversible or irreversible
134
define competitive antagonist
an antagonist competes with agonists for the same receptor binding site
135
How do reversible antagonists work?
increasing agonist concentration can outcompete antagonist
136
How do irreversible antagonists work?
they permanently bind to receptors, so no amount of agonist can dislodge it
137
How do reversible antagonists affect concentration-response curves of an agonist?
curve to the right but still can reach Emax, as a higher concentration of agonist A is needed to give the same response
138
How do reversible antagonists affect Emax and EC50?
Emax of the agonist stays the same, but EC50 of agonist increases
139
How do irreversible antagonists affect concentration-response curves of an agonist?
curve will be lower and to the right
140
How does an irreversible antagonist affect Emax and EC50 of an agonist?
Emax of agonist decreases, EC50 of agonist increase
141
How do we measure antagonism?
using the Schild plot and PA2
142
define Schild plot
a way to determine the nature and potency of an antagonist
143
What are the axes on a Schild plot?
X axis -> log (concentration of antagonist)
Y axis -> log (dose ratio -1)
144
What is the equation for dose ratio?
EC50 of agonist with antagonist / EC50 of agonist without antagonist
145
How do you determine the pA2 value?
pA2 vaule is where the line on the Schild plot intersects the X-axis (remember it is negative log of concentration)
146
What does pA2 measure?
antagonist potency
147
What is the pA2 equation?
pA2 = log(dose ratio -1) - log[antagonist]
148
What does a higher pA2 value indicate?
a more potent antagonist
149
What is indicated if two antagonists give the same pA2 value?
they act through the same receptor
150
Where do agonists and competitive antagonists bind on a receptor?
the orthosteric site
151
What is the allosteric site and its function?
another site on the receptor -> other molecules can bind here and modify the effects of an agonist
152
define affinity modulation
the process of altering how well the agonist binds to the orthosteric site
153
define efficacy modulation
the process of altering how well the agonist activates the receptor
154
define affinity allosteric modulator
a ligand that binds to a receptor and alters how well the AGONIST binds to the receptor at the orthosteric site
155
What do positive affinity allosteric modulators do?
increase how well an agonist binds to the orthosteric site, and decreases the concentration needed for the same reponse
156
What do negative affinity allosteric modulators do?
decrease how well an agonist binds to the orthosteric site, and increase concentration needed for the same response
157
define efficacy allosteric modulator
a ligand that binds to a receptor and alters how well the agonist activates the receptor -> the full response of the agonist will be increased or decreased
158
define allosteric agonist
an allosteric ligand that binds to a receptor and can cause a response on its own without need for an agonist
159
What type of cells are neurones?
postmitotic
160
define postmitotic
cells that are fully differentiated and unable to divide
161
define soma
the cell body of a neurone, an expanded area of cytoplasm where nucleus and organelles are found
162
Which organelle do neurones NOT have?
centrioles -> important in cell division, so don't need them
163
What is the structure and function of the myelin sheath?
made up of Schwann cells and they insulate the axon
164
What are the 4 shape classes of neurones?
multipolar, bipolar, unpolar, anaxonic
165
What are the 3 classes of neurones?
afferent, efferent, interneurone
166
define afferent neurone
transmits signal from receptors to CNS
167
define efferent neurone
transmits signal from CNS to effectors
168
define interneurone
transmits signal from afferent to efferent neurones
169
What is a resting membrane potential (RMP)?
an electrical charge across the plasma membrane, with the interior of the cells negative compared to exterior
170
define chemical gradient
gradient based on concentration
171
define electrical gradient
gradient based on charge
172
What are the 2 types of movement across the plasma membrane involving proteins?
facilitated diffusion and active transporters (pumps)
173
define facilitated diffusion
when ions diffuse down their concentration gradient and the channels are selectively permeable to different ions
174
define active transport
when pumps move ions against their concentration gradient and create a concentration gradient across the membrane
175
How do Na+ and K+ pumps maintain excitability?
active transporters exchange 2K+ in for every 3NA+ out
176
What is the resting membrane potential in most neurones?
-70mV
177
Which equation is used to calculate the equilibrium potential for an ion?
the Nernst equation
178
give the Nernst equation
E ion = RT / zF x log [ion]outside / [ion]inside
179
Which other equation is used to calculate the resting membrane potential?
Goldman equation
180
define action potential
a brief change in the voltage across a membrane due to the flow of ions into and out of the neurone
181
What does the 'all or nothing law' describe?
if a stimulus is strong enough, an action potential occurs, which is always a full response i.e. can't be strong or weak
182
What are the 5 phases of action potentials?
1. hypopolarisation
2. depolarisation
3. overshoot
4. repolarisation
5. hyperpolarisation/undershoot
183
define hypOpolarisation
the initial increase of the membrane potential to the value of threshold potential
184
define depolarisation
the potential moving from the RMP to less negative values
185
define overshoot
the peak of the action potential being reached at about +40mV
186
define repolarisation
the potential moving back to the RMP (-70mV)
187
define hyperpolarisation/undershoot
the potential moves away from the RMP in a MORE negative direction, but the RMP is eventually restored due to K leak channel and sodium-potassium pump
188
action potential stage 1
membrane is at resting potential and VGNC and VGKCs remain closed
189
action potential stage 2
a stimulus causes depolarisation the threshold potential and VGNCs open
190
action potential stage 3
Na+ ions flow in and the membrane rapidly depolarises and more VG sodium ion channels open but VGKCs remain closed
191
action potential stage 4
VG sodium ion channels are inactivated and Na+ entry slows
192
action potential stage 5
VGKCs open and K+ begin to flow out, beginning repolarisation
193
action potential stage 6
VGNC channels fully close and VGKC remain open to give delayed hyperpolarisation -> eventually resting potential is restored
194
What are the properties of VGNCs?
1. open rapidly with depolarisation at around -55mV
2. moving away from -55mV causes inactivation
3. inactivated channels are blocked during continued depolarisation
4. inactivated channels move to a closed state during repolarisation
195
What are the properties of VGKCs?
1. K+ channels slowly open during depolarisation at about +30mV
2. they close slowly on repolarisation
196
What are the 2 classes of refractory period?
absolute refractory period, relative refractory period
197
What happens during the absolute refractory period?
action potentials cannot be generated as VGNCs are inactivated and can't be activated again until the membrane is repolarised and resting state is restored
198
When does the refractory period occur?
from the start of an action potential to the point that voltage first returns to RMP
199
What happens during the relative refractory period?
the membrane potential is hyperpolarised by VGKCs and action potentials CAN be generated if the stimulus is strong enough to overcome hyperpolarisation and reach threshold
200
What is action potential propagation?
the process by which an action potential travels across a neurone
201
How does action potential propagation work (local currents)?
1. stimulation at point A exceeds threshold
2. local currents spread along axon and exceed threshold
3. this opens VGNC and generate AP at point B
4. VGNC inactivation occurs and open VGKC prevent back-propagation
202
What 2 factors does the velocity of action potential propagation depend on?
1. axon diameter
2. myelination
203
How does axon diameter affect action potential propagation velocity?
the larger the diameter, the faster the propagation as there is more space for ions to travel
204
define saltatory conduction
the propagation of action potentials along myelinated axons from one node of Ranvier to the next, increasing velocity
205
What causes Guillain-Barre syndrome?
the destruction of Schwann cells in the peripheral nervous system
206
What causes multiple sclerosis (MS)?
a loss of oligodendrocytes in the brain and spinal column
207
What are the 2 types of graded potential?
excitatory and inhibitory
208
What do inhibitory graded potentials do?
take the membrane further away from the threshold potential
209
What are the 4 types of excitatory graded potentials?
1. temporal summation
2. spatial summation
3. no summation
4. spatial summation of EPSPs and IPSPs
210
define temporal summation
2 excitatory stimuli close in time causes EPSPs to add together
211
define spatial summation
2 simultaneous stimuli at different locations cause EPSPs to add together
212
define no summation
2 stimuli separated in time cause EPSPs that do NOT add together
213
define spatial summation of EPSPs and IPSPs
changes in membrane potential that cancel each other out
214
define synapse
the point at which an electrical signal moves from one nerve cell to another
215
What are the 2 types of synapse?
electrical and chemical
216
What is the structure of an electrical synapse?
the pre and post-synaptic neurones are directly connected by gap junctions
217
What is the structure of an chemical synapse?
the pre and post-synaptic neurones are physically separated by the synaptic cleft and chemical transmitter from pre-synaptic neurone binds to receptors on post-synaptic neurone
218
What are gap junctions?
channels formed by connexons in both cell membranes and allow direct passage of ions and small molecules through the channels
219
What are the features of chemical synapses?
1. synaptic vesicles filled with neurotransmitter on the inside of the presynaptic neurone
2. voltage-gated calcium ion channels in presynaptic neurone
3. neurotransmitter receptors on postsynaptic neurone
220
What are the 3 types of synapse in the CNS?
axo-dendritic, axo-somatic, axo-axonal
221
define axo-dendritic synapse
an axon synapsing onto a dendrite
222
define axo-somatic synapse
an axon synapsing onto a cell body
223
define axo-axonal synapse
an axon synapsing onto another axon or axon terminal
224
define neurotransmitter
a chemical messenger that is released from a pre-synaptic neurone
225
What are the sequence of events involved at a chemical synapse?
1. neurotransmitter is synthesised and stored in vesicles
2. AP arrives at presynaptic terminal
3. AP depolarises the terminal and VGCC opem
4. Ca2+ enter and trigger exocytosis
5. transmitter diffuses down synaptic cleft and binds to receptors
6. ion flow causes postsynaptic response
7. transmitter is removed by enzyme breakdown or reuptake
8. the vesicle is retrieved from the terminal membrane
226
What are the 4 key criteria for a substance being a neurotransmitter?
1. substance must be present within the presynaptic neurone
2. substance must be released in response to presynaptic depolarisation by an AP
3. specific receptors for the substance must be present on the postsynaptic cell
4. there must be a mechanism for removal and/or breakdown
227
What are the 2 types of neurotransmitter receptor?
ionitropic receptor, metabotropic receptor
228
What is an ionotropic receptor?
a ligand (transmitter) gated ion channel that opens to allow passage of ions through membrane in response to binding
229
What is a metabotropic receptor?
a g protein-coupled receptors -> binding activates g-protein which activates second messenger which can directly affect ion channels on membrane
230
What is a neuromuscular junction?
the synapse between a motor neurone and skeletal muscle
231
What is a neuromuscular junction also known as?
a motor endplate
232
Which neurotransmitter and receptor are used at neuromuscular junctions?
acetylcholine and nicotinic receptors
233
What type of receptor in the nicotinic acetylcholine receptor?
ionotropic or neurotransmitter-gated ion channel
234
How is acetylcholine synthesised?
in the presynaptic terminals by the enzyme choline acetyltransferase
235
How is acetylcholine broken down?
by acetylcholinesterase into acetate and choline
236
What is the main excitatory transmitter in the CNS?
glutamate
237
What type of receptor does glutamate activate?
both ionotropic and metabotropic receptors
238
What is the main inhibitory transmitter in the CNS?
GABA (G-aminobutyric acid)
239
What type of receptor does GABA work on?
a small family of ionotropic and metabotropic receptors
240
What type of potential does glutamate generate?
an excitatory postsynaptic potential (EPSP)
241
What type of potential does GABA generate?
an inhibitory postsynaptic potential (IPSP)
242
What do IPSPs do?
make a neurone less likely to generate an action potential
243
define gastrointestinal system
a network of organs and specialised cells that enable you to transform food into the energy and nutrients required for life
244
Which organs is the GI tract made up of?
mouth, oesophagus, stomach, small intestine, large intestine, anus
245
Name the accessory organs
salivary glands, liver, gallbladder, pancreas
246
define accessory organ
an organ that plays a role in the function of the GI tract but is not part of it
247
define mesentery
a membranous tissue that surrounds the organs of the GI tract
248
What is the function of the mesentery?
- holds intestines in place
- has lots of blood vessels and lymphatics for absorption and immunity
249
What prevents food travelling to the lungs?
the pharynx and epiglottis
250
What is the function of the oesophagus?
to transport food bolus to the stomach
251
What are the main functions of the stomach?
- mix food
- digest protein
- emulsify fat
252
How many layers is the stomach wall made up of?
4
253
Which cells is the stomach acid produced by?
parietal cells
254
Which 3 sections is the small intestine divided into?
duodenum, jejunum, ileum
255
What is the function of the small intestine?
primary site of absorption
256
What increases the surface area of the small intestine?
finger-like projections called villi that contain microvilli with epithelial cells on surface
257
Which 3 sections is the small intestine divided into?
ascending colon, transverse colon, descending colon
258
What is the function of the large intestine?
- role in conservation of water and ions
- storage of faecal matter
- crypts that are involved in lysosome secretion
259
How many sets of salivary glands do humans have?
3
260
What is the function of saliva?
- contains some digestive enzymes
- lubricates food with mucus
261
What is the function of the liver in digestion?
- produces bile and involved in excretion
- bile is needed for emulsification of fats
262
What is the function of the gallbladder?
- collects secretions from liver
- delivers bile to duodenum
263
What is the function of the pancreas?
- makes enzymes to digest proteins, fats, carbohydrates
- produces insulin and glucagon from islets of Langerhans
264
What are the 4 functions of the GI system?
1. ingestion
2. secretion
3. movement
4. digestion
265
define ingestion
the process of taking in food or drink through the mouth
266
define secretion
the release of substances that contribute to digestion
267
What are the 2 main types of movement in the GI system?
segmentation and peristalsis
268
define segmentation
'squishing' of substances backwards and forwards to help move them
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define peristalsis
coordinated movement with contraction and relaxation of intestine
270
define digestion
breakdown of food into smaller components that can be absorbed into the bloodstream
271
What are the 2 types of digestion?
mechanical and chemical
272
define absorption
the process through which nutrients, water and electrolytes enter the blood (through villi and microvilli)
273
define excretion
the process by which metabolic waste is eliminated from the body
274
Which 2 main parts is the nervous system divided into?
the central and peripheral nervous systems
275
What is the central nervous system made up of?
the brain and spinal cord
276
define periphery
the area that is away from the centre of the body
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define afferent neurone
a neurone that transmits an action potential from the periphery to the CNS
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define efferent neurone
a neurone that transmits an action potential from the CNS to the periphery
279
define vertebrae
a stack of bones that surround the spinal cord
280
What are the 4 sections of spinal nerves that receive inputs and send outputs?
cervical, thoracic, lumbar, sacral
281
How do sensory inputs enter the CNS?
through the dorsal root into the spinal cord
282
What is the dorsal root ganglion?
where the cell bodies of axons are just outside the vertebrae in the spinal cord
283
What type of neurone are most sensory neurones?
unipolar -> have a cell body and one long axon
284
What is the simplest example of a connection between sensory neurone input and output back to the periphery?
the monosynaptic reflex
285
define monosynaptic
there is ONE synapse between the presynaptic and postsynaptic neurone
286
What type of neurone are most motor neurones?
multipolar
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define reflex
when input is received by the periphery and the body provides output back to the periphery without any conscious thought
288
What do proprioceptors do?
sense position and movement
289
How does the knee jerk reflex work?
1. tap the tendon attached to the quadriceps
2. the tendon gets pulled, which stretches the quadriceps
3. this is sensed by the muscle spindle fibres (proprioceptors)
4. generates action potential
5. action potential goes through dorsal root to spinal cord
6. neurotransmitter is released in spinal cord
7. this causes an action potential in a motor neurone, which causes the quadriceps to contract
290
What is the pathway of a reflex arc?
1. receptor gives input to integrative centre
2. integrative centre gives output to effector
291
What is USUALLY the integrative centre?
the spinal cord
292
How do sensory neurones vary?
by thickness and myelination
293
What does the extent of myelination determine?
the speed of an action potential
294
define ascending pathway
neuronal input travelling from the spinal cord to the brain
295
give an example of an ascending pathway in proprioception
1. action potential comes into dorsal root
2. goes up the spinal cord to a synapse at the brain stem (medulla)
3. action potential crosses to the other side of the body
4. it reaches another synapse in the middle of the brain called the thalamus
5. eventually reaches the somatosensory cortex
296
define descending pathway
information going from the brain to the spinal cord
297
Where does all input from the periphery to the CNS BELOW the neck go to?
the spinal cord
298
Where does all input from the periphery to the CNS go to if ABOVE the neck?
the cranial nerves
299
define glial cell
a cell that is specialised to help neurones function but are NOT neurones
300
What are 2 examples of glial cells?
oligodendrocytes and astrocytes
301
What do oligodendrocytes do?
produce myelin -> there are different glial cells that do this in the peripheral nervous system called Schwann cells
302
What does astrocytes do?
act as a buffer to equalise concentrations of k+ ions -> there may be high concentrations of K+ ions if axons are generating many action potentials, so astrocytes 'suck them up' and move them to other parts of the brain
303
define the meninges
the 3 layers of membranes that cover and protect the brain and spinal cord
304
What is the outer membrane called?
dura mater
305
What is the inner membrane called?
the pia mater
306
What is the space between the inner and outer membranes called?
the sub arachnoid space
307
What is the sub arachnoid space filled with?
cerebrospinal fluid
308
What is the function of the choroid plexus?
it is a gland in the middle of the brain that produces cerebrospinal fluid
309
What does the cerebrospinal fluid contain?
salt and sugar -> high concentrations of Na+ and low K+ -> glucose and oxygen
310
What is the blood-brain barrier?
a semipermeable membrane separating the blood from the cerebrospinal fluid and brain
311
What is the structure of the blood-brain barrier?
tight junctions between the endothelial cells and blood vessel wall (tight junction is a seal between two cells that prevents leakage of content)
312
What does the blood-brain barrier do?
prevents substances leaking out of the blood vessels into the brain, including blood borne viruses and bacteria
313
Which cells acts as immune cells in the brain?
microglia
314
What are the 3 main characteristics of skeletal muscle?
1. made up of fibres
2. mutlinucleate
3. attached to bone
4. controls posture and movement
5. voluntary control
6. antagonistic sets of muscle
315
How do the multi-nucleate muscle cells form?
fusion of muscle cells during embryonic growth
316
define tendon
bundles of collagen fibres that attach muscle to bone
317
define myofibril
bundles of actin and myosin filaments that make up muscle cells
318
What is the main function of the sarcoplasmic reticulum?
stores calcium in vesciles which is important to release Ca2+ ions in response to signals from the nervous system
319
What are the 5 main components of sarcomeres?
1. thin filaments
2. thick filaments
3. z-lines
4. H zone
5. M-line/discs
320
What are the thin filaments composed of?
actin, troponin and tropomyosin
321
Which band do the thin filaments make up?
the I band
322
What are the thick filaments composed of?
myosin and titin
323
What is the function of titin?
to act as a scaffold for the sarcomere
324
Which band do the thick filaments make up?
the A band
325
What are the Z-lines?
a network of proteins that hold the thin filaments (actin) in place and together
326
What are the Z-lines composed of?
alpha-actinin
327
What is the H zone?
a light area in the centre of the A band of a sarcomere that contains only thick filaments and NOT thin actin filaments
328
What are M-lines/discs?
proteins that link the central regions of the thick filaments
329
What is the M-line composed of?
myomesin
330
What is the structure of each myosin molecule?
1. has a light and heavy chain that are intertwined
2. has a double globular head
3. half the head is facing the left, and half to the right
4. the area between the double head is known as the M-region
331
What is the structure of each actin subunit?
1. each subunit has an active site than can bind to the head of a myosin molecule
2. tropomyosin is wound around eahc subunit
3. tropomyosin is held in place by the calcium-binding protein troponin
332
How do the Z-lines work?
the alpha-actinins bind and cross-link the ends of F-actin filaments from adjacent sarcomeres at the Z line
333
What is the interaction between actin and myosin filaments regulated by?
troponin
334
How many types of troponin are there? What are they?
1. Troponin I -> inhibitory
2. Tropnin C -> calcium binding
3. Troponin T -> tropomyosin binding
335
What happens when calcium binds to troponin C?
causes a conformational change that moves tropomyosin aside to expose the actin binding site that binds to the myosin head
336
What are the 3 main steps of skeletal muscle contraction?
1. resting muscle state
2. activation of contraction
3. breaking the cross-bridge
337
What are the steps of the resting muscle state?
1. energised myosin is bound to ADP and Pi
2. tropomyosin covers the myosin binding sites on the actin filaments and prevents interaction
338
What are the steps of activating contraction?
1. muscle stimulated by action potentials and cytosolic calcium levels increase
2. calcium binds to troponin and moves it aside exposing myosin binding sites on actin
3. the energised myosin molecule and ADP bind to actin
4. the cross-bridge formation causes the release of ADP and Pi and movement of the crossbridge to cause contraction
339
What are the steps of breaking the cross-bridge?
1. ATP binds to myosin and breaks the cross-bridge
2. ATP is converted to ADP and myosin returns to its energised position
340
define motor end plate
the region of the muscle fibre directly under the terminal portion of the axon of the neurone at the neuromuscular junction
341
Which two components make up the neuromuscular junction?
the motor end plate + axon terminal
342
How does an action potential stimulate a muscle?
1. action potentials in the motor neurone depolarise the axon terminal
2. this opens voltage-gated calcium ion channels
3. Ca2+ ions enter the cell and trigger release of acetylcholine from vesicles
4. Ach diffuses and activates nicotinic acetylcholine receptors
5. this causes depolarisation of the motor end plate causing an endplate potential
343
What are the steps of calcium release from the sarcoplasmic reticulum?
1. an action potential in the muscle is propagated
2. Ca2+ is released from the lateral sac
3. Ca2+ binding to troponin removes the blocking action of tropomyosin
4. the cross-bridge moves
5. Ca2+ is taken up
6. Ca2+ removal from troponin restores tropomyosin's blocking action
344
What are the 2 main types of skeletal muscle fibres?
fast twitch fibres and slow twitch fibres
345
What are the features of fast twitch fibres?
1. contract rapidly
2. get energy from glycolysis
3. anaerobic
4. used for explosive power such as sprinting and powerlifting
346
What are the features of slow twitch fibres?
1. contract slower
2. get energy aerobically
3. used for long periods of activity such as long-distance running
4. fatigue resistant
347
How does genetic variation affect athletic performance for some?
1. alpha-actinin 3 is expressed in a subset of fast twitch muscles
2. a genetic variant encodes an early stop codon and causes a truncated form of alpha-actinin 3
3. causes high performance in long distance running
348
What are features of cardiac muscle cells?
1. single, polyploid nucleus
2. striated pattern
3. cells electrically connected by intercalated discs
4. cells have 2 types of electrical activity -> pacemarker and cardaic action potentials
5. heart rate is regulated by catecholamines
349
What causes the nucleus in cardiac cells to be polyploid?
nucleus has undergone extra DNA replication without the cell dividing
350
Where are the intercalated discs located?
the Z-line of the sarcomeres that hold the actin filaments together
351
What are the 3 types of intercalated discs?
1. interdigitating folds
2. mechanical junctions
3. electrical junctions
352
define interdigitating fold
infolds at the end of cardiac cells that increase the surface area of cell-cell connection
353
What are the 2 types of mechanical junctions in cardiac cells?
Adherens junctions and desmosomes
354
What do Adherens junctions do?
join the cell membrane to the actin filaments of the cardiomyocytes to help the transmission of contractile force between different cells
355
What do desmosomes do?
give strong structural support between cardiomyocytes to ensure they can withstand the contractile forces
356
What are the electrical junctions in cardiac muscle called?
gap junctions
357
What is the function of gap junctions?
they allow the transmission of ions between cells allowing depolarisation
358
What are gap junctions made of?
a hexamer composed of connexins provided by each cell --> hexamers are shared between cells to form a gap junction with 12 subunits connecting the cells
359
Are cardiac pacemaker cells initiated by nerve stimulation?
no, but can be modified by stimuli from the autonomic nervous system
360
How do pacemaker cells generate cardiac action potentials?
they generate their own spontaneous ones
361
Where are the primary pacemaker cells?
in the sinoatrial node (SAN)
362
What are the steps of generating a pacemaker action potential?
1. phase 4: a channel called the funny channel opens and allows influx of Na+ ions, causing a GRADUAL increase in membrane potential
2. phase 0: T-type calcium ion channels open and allow influx, causing a rapid depolarisation of the membrane
3. phase 1: voltage-gated K+ channels open and cause rapid repolarisation and K+ ions leave the cell
4. the cycle repeats
363
What are the steps of generating cardiac muscle cell action potentials?
Phase 4: cells at resting potential known as diastole
Phase 0: voltage-gated Na+ ion channels open due to arrival of action potential from the neighbouring cell, allowing rapid influx of Na+ ions, causing rapid depolarisation
Phase 1: rapid inactivation of Na+ channels and opening and closing of K+ channels causes a very brief efflux of K+ ions as they leave, causing a 'notch' on the graph
Phase 2: plateau as the membrane potential remains relatively constant as the membrane is slowly repolarising
L-type Ca2+ channels allow Ca2+ ions to enter the cell after they are activated by sodium influx in phase 0
Phase 3: rapid repolarisation as L-type Ca2+ ion channels close and voltage-gated K+ channels open
364
Which factors increase heart rate from the SA node?
increased plasma adrenaline, increased sympathetic nerve activity
365
Which factors cause a decrease in heart rate from the SA node?
increase in parasympathetic nerve activity
366
How does Ca2+ release during the cardiac action potential cause more Ca2+ release? (calcium induced calcium release)
1. L-type calcium channels open during the cardiac action potential
2. small amounts of Ca2+ enter the cell to trigger the opening of Ryanodine Receptor calcium channels in the sarcoplasmic reticulum
3. Ca2+ is released from the sarcoplasmic reticulum and binds to troponin to trigger cross bridge cycling
4. Ca2+ is returned back into the sarcoplasmic reticulum by the sarco/endoplasmic reticulum calcium ATPase (SERCA)
5. Na+/Ca2+ exchanger removes calcium out of the cell
6. the membrane is repolarised by potassium channels at the end of the action potential
367
How is a myocardial infarction detected?
cardiac troponins are fragmented and released into the blood when the heart muscle is damaged
368
What is dilated cardiomyopathy (DCM)?
a heart condition caused by the left ventricle dilating, making it harder to pump blood around
369
What is DCM caused by?
mutations in genes including those encoding actin, myosin, alpha-actinin, titin or troponin
370
What are symptoms of DCM?
shortness of breath and fatigue as the left ventricle fails
371
What are the differences between skeletal msucle and smooth muscle?
- smooth muscle cells are much smaller than skeletal muscle cells
- less organised actin-myosin arrangement
- contraction is regulated by calcium binding to calmodulin, NOT troponin
372
Where is smooth muscle found?
tubular and hollow organs such as the airways, arteries, veins, intestines, uterus etc
373
What does relaxation of vascular smooth muscle cause?
vasodilation, increasing blood supply to the tissues
374
What does contraction of vascular smooth muscle cause?
vasoconstriction, decreasing blood supply to the tissues
375
What is the structure of smooth muscle in the intestine?
longitudinal and circular layer
376
Which layer of the stomach is made up of smooth muscle?
muscularis externa
377
What is the structure of smooth muscle in the stomach?
3 layers:
- inner oblique layer churns food and is responsible for mechanical digestion
- circular layer form the pyloric sphincter and controls flow of stomach contents into the duodenum
- longitudinal layer moves food towards the pylorus
378
What are the POSSIBLE functions of smooth muscle in the trachea and bronchia?
1. peristalsis for expiration
2. even distribution of airflow during ventilation
3. supporting airway wall
4. enhancing coughing
379
What are the 2 types of smooth muscle?
single unit and multi unit
380
What are the features of single unit smooth muscle?
1. made of fibres in sheets
2. cells connected by gap junctions
3. muscle contracts as a syncytium
381
What are the features of multi unit smooth muscle?
1. cells act as individual units
2. few or no gap junctions
3. allows fine grain control
382
What does smooth muscle have instead of Z-lines?
dense bodies
383
What do dense bodies do?
hold actin thin filaments allowing them to exert force -> they are attached to the sarcolemma by intermediate filaments
384
What are the 2 sources of calcium ions for smooth muscle contraction?
internal calcium stores and external influx through calcium ion channels
385
What is the calcium binding protein in smooth muscle?
calmodulin
386
What are the 3 major steps of smooth muscle contraction?
1. resting muscle state
2. activation of contraction
3. breaking the cross bridge
387
What are the steps of the resting muscle state?
1. the dephosphorylated myosin head group is held close to the myosin filament
388
What are the steps of activating contraction?
1. the muscle is stimulated by neurotransmitters and cytosolic calcium levels increase
2. calcium binds to calmodulin
3. calcium-calmodulin complex binds to myosin light chain kinase (MLCK)
4. MLCK is activated
5. active MLCK uses ATP to phosphorylate the myosin light chains in the myosin head group
6. this causes to cross bridge to move away from the thick filament to a position where it can bind to actin
389
What are the steps of breaking the cross-bridge?
1. myosin is dephophorylated by myosin light chain phosphatase
2. when Ca2+ levels are high, activity of MLCK is greater than MLCP activity, so myosin gets phosphorylated
3. now Ca2+ levels have decreased, so MLCP activity is greater than MLCK, so myosin is dephosphorylated
390
How is the sarcoplasmic reticulum a source of calcium ions?
1. action potentials can release Ca2+ stores from the SR near the plasma membrane
2. second messengers can release Ca2+ stores from the SR
391
How does the muscle cell get Ca2+ from extracellular sources?
influx through voltage-gated Ca2+ channels in the plasma membrane
392
How is smooth muscle contraction in the GI tract initiated?
1. slow waves are generated by pacemaker cells called interstitial cells of Cajal
2. slow waves spread to the surrounding smooth muscle cells via gap junctions
393
How is contraction of smooth muscle through neurones stimulated?
varicosities release neurotransmitters that cause smooth muscle cells to contract or relax
394
define varicosity
an axon-like swelling of autonomic neurones that form motor units in smooth muscle
395
What are the differences between acetylcholine receptors in skeletal muscle compared to smooth muscle?
skeletal muscle= the nicotinic receptor activated by acetylcholine is an ion channel receptor
smooth muscle= the muscarinic receptor activated by acetylcholine is a G protein-coupled receptor
396
What are the steps of releasing internal Ca2+ stores after GPCR activation?
1. trimeric G-protein with alpha, beta and gamma subunits
2. activation of the GPCR activates the alpha subunit of the G protein by GDP/GTP exchange
3. this causes dissociation of the alpha subunit bound to GTP from the beta-gamma subunit
4. the GTP bound alpha subunit activates phospholipase C
5. phospholipase C cleaves PIP2 into IP3 and DAG
6. IP3 binds to IP3 receptors in the sarcoplasmic reticulum and opens calcium ion channels
7. Ca2+ ions are released from the sarcoplasmic reticukum
397
What are the 2 main receptors in smooth muscle?
alpha-1 adrenergic receptor and beta-adrenergic receptor
398
What does alpha-1 adrenergic receptor do?
mediate constriction in most vascular smooth muscle
399
What does beta-adrenergic receptor do in smooth muscle?
mediate dilation of vascular smooth muscle and lung airway smooth muscle
400
How is asthma and COPD commonly treated?
1. M3 muscarinic receptors control bronchioconstriction in the airways (hypersenstitive)
2. beta-adrenergic receptors control smooth muscle relaxation and bronchiodilation
3. beta-adrenergic agonists are used to treat asthma and COPD
401
define atherosclerosis
thickening or hardening of the arteries caused by a buildup of plaque in the inner lining of an artery
402
