Week 5, Lecture 2 Flashcards
(127 cards)
1
Q
SERCA (Sarcoplasmic/Endoplasmic Reticulum Calcium ATPase) does what
A
regulating calcium reuptake into the sarcoplasmic reticulum (SR) after a contraction.
2
Q
decreased SERCA activity in cardiac myocytes would?
A
- impair calcium reuptake, leading to prolonged muscle relaxation (diastolic dysfunction)
- reduced calcium release for contraction, causing weaker heartbeats (negative inotropy).
- Over time, this could lead to heart failure due to decreased cardiac output and hypertrophy, as well as an increased risk of arrhythmias due to calcium imbalance.
3
Q
SERCA for…
A
muscle relaxation (Ca2+ back into SR)
In skeletal and cardiac muscle cells, SERCA plays a key role in muscle contraction and relaxation. When a muscle is stimulated, calcium is released from the SR, triggering contraction. SERCA then removes Ca²⁺ back into the SR, allowing the muscle to relax.
4
Q
how does skeletal myocyte excitation contraction coupling happen
A
sarcolemma:
1. acetylcholine –> open nicotinic receptor –> initial depolarize
2. Na+ VGC open –> depolarize sarcolemma (AP) –> open Ca2+ VGC
3. L type Ca2+ VGC open ryanodine receptor in SR –> T tubules to get AP deep in cytsool
4. increased systolic Ca2+ binds troponin (move away tropomyosin) –> lets myosin bind actin
5. cross bridge + contract
6. Ca2+ levels decrease (pump Ca2+ into ECF or SR)
7. tropomyosin covers myosin binding site and sarcomere relaxes
5
Q
what is main role of L-type Ca2+ VGC
A
lets a little bit of Ca2+ into cell but MAIn action is open ryanodien receptor in SR
6
Q
where does most of the calcium that enters the cytoplasm come from
A
SR
7
Q
cross bridge cycle events
A
- ADP+Pi bound to myosin head (allosterically blocked by tropomyosin)
- calcium binds troponin C so that tropomyosin is removed and that actin can bind myosin;; release ADP and Pi
- change conformation
- recoil and power stroke
5.rigor state - ATP binds myosin head, which causes detachment of actin
- back to resting
8
Q
what causes striated appearance of skeletal and cardiac muscle
A
thick and thin filament overlap
9
Q
thick and thin filaments which is which
A
thick= myosin
thin= actin
- overlap between thick (myosin) and thin (actin) filaments for proper muscle contraction.
- This overlap enables the formation of cross-bridges between myosin and actin, which is crucial for generating muscle tension during contraction.
10
Q
A band vs I band vs H zone
A
A band= thick and thin
I band= thin (actin) only
H zone= thick (myosin) only
11
Q
partial tetanus
A
- When the interval between successive activations shortens such that individual twitches do not relax completely between successive action potentials; peak muscle tension increases but oscillates.
vs normal: individual muscle twitches in response to single action potentials; the second action potential occurs after complete muscle relaxation from the first action potential
12
Q
tetanus
A
- As the interval between successive stimuli decreases more, twitches fuse on top of one another resulting in a sustained generation of force many times greater than a single twitch.
▪ APs are too frequent to allow clearance of calcium from the cytosol
vs normal: individual muscle twitches in response to single action potentials; the second action potential occurs after complete muscle relaxation from the first action potential
13
Q
what does increased cytotoxic calcium causes
A
more myosin engaged with actin –> increased force development
14
Q
similarities between skeletal and cardiac myocytes
A
- Striated, involve actin: myosin overlap
- Parabolic isometric length: tension relationship
- Peak isometric forces matches optimum passive resting length
- T-tubules exist in both
- Ca2+ ATPase pumps to remove Ca2+ into SR
15
Q
what happens in muscles cells with fusing of twitches and not enough time to clear Ca2+ from cytosol that cannot happen in cardiac myocytes
A
tetany
- No tetanic contraction in cardiac myocytes due to long electrical refractory period
16
Q
why do cardiac myocytes not have tetany
A
long electrical refractory period
17
Q
what is a sanctum in cardiac myocytes
A
Syncytium: cardiac myocytes are interconnected via branches and intercalated disks (gap junctions and desmosomes)
- T tubules play a less important to the excitation- contraction coupling of cardiac cells; they are larger but fewer
18
Q
how many nuclei and mitochondria in cardiac cells
A
Cardiac cells have 1 single nucleus and LOTS of mitochondria
19
Q
what is a parabolic isometric length-tension relationship
A
- Both cardiac and skeletal muscles exhibit a parabolic length-tension relationship, meaning the force generated by the muscle depends on its length.
- There is an optimal muscle length (sarcomere length) where the overlap between actin and myosin filaments is ideal, generating the greatest force.
- If the muscle is too stretched or too compressed, the force production decreases
20
Q
t tubules in both cardiac and skeletal myocytes
A
- Both cardiac and skeletal muscles have T-tubules (transverse tubules), which are invaginations of the sarcolemma (muscle cell membrane).
- They help propagate action potentials deep into the muscle fibers, ensuring that the excitation reaches the myofilaments in the interior of the muscle cell for synchronized contraction.
21
Q
SERCA pumps in both cardiac and skeletal muscle fibers in SR for
A
- These pumps actively transport calcium back into the SR after a contraction, reducing intracellular calcium levels and allowing muscle relaxation.
- Proper regulation of calcium is criQcal for the contraction-relaxation cycle.
22
Q
why do cardiac myotcytes not have titanic contraction?
A
- Cardiac muscle cells cannot undergo tetanic contraction (sustained contraction) because they have a long electrical refractory period.
- This long refractory period prevents another action potential from being initiated immediately after the first, ensuring that cardiac muscle relaxes fully between beats and avoids dangerous sustained contraction, which is crucial for proper heart function.
23
Q
syncytium in cardiac myocytes
A
- Cardiac muscle cells function as a syncytium, meaning the cells are interconnected through branches and intercalated disks.
- The intercalated disks contain gap junctions (allowing ions to flow directly between cells) and desmosomes (providing structural support), which enable coordinated contraction across the entire heart, making it function as a unified organ.
- This is unlike skeletal muscle, where each fiber contracts independently.
24
Q
t tubules have less central role in cardiac muscle
A
- While T-tubules exist in both cardiac and skeletal muscle, they play a less critical role in cardiac muscle’s excitation-contraction coupling. In cardiac myocytes, the T-tubules are larger but fewer in number.
- Cardiac cells rely more on extracellular calcium influx (through L-type calcium channels) than skeletal muscle, where the T-tubule system is more integral for calcium release from the SR.
25
how many nuclei and mitochondria in skeletal muscle fibers vs cardiac
skeletal are multinucleated, less mitochondria
single nucleus in cardiac myocytes and higher density of mitochondria to meet energy demands of continuous rhythmic contraction
26
how are adjacent cardiomyocytes connected together
gap junctions crossing intercalated disks in a synctium
27
synctium
all cells electrically connected (via gap junctions and intercalated disks) in cardiomyocyte
28
4 phases of action potentials
▪ Phase 4 – resting membrane potential (RMP)
▪ Phase 0 – the rapid depolarization phase (upstroke)
▪ Phase 1 & 2 – prolonged depolarization/plateau phase
▪ Phase 3 - repolarization
29
atrial and ventricular action potentials
Both have distinct phases of depolarization, plateau, and repolarization, but atrial APs are shorter, allowing for faster contraction cycles.
30
what action potentials are purkinje cells similar to
ventricular
Similar to ventricular APs but with a slightly unstable phase 4, giving them the ability to spontaneously generate action potentials in abnormal conditions.
31
automatic cell/ pacemaker (SA and AV node) action potential have what
unstable phase 4 and depolarize spontaneously due to the funny current (If), setting the heart rate through automatic, rhythmic action potentials.
32
action potential are ___ events of the ____
electrical events of the sarcolemma
▪ Flow of ions across the cell membrane through channels down their electrochemical gradient
▪ Gradients mostly established by pumps
33
action potential cause contraction and force development indirectly but ___ measures of contraction
ARE NOT
they are electrical events, not force generation
34
what is the Nernst potential of a resting membrane potential
-84 mV
35
phase 4- RMP- what channels are open
k+ leak channels
36
phase 0- rapid depolarize what channels open
Na+ V gated channels
37
phase 1- transient repolarization; what channels open and close
na+ VGC close
K+ channels open; efflux
38
phase 2 what channels open
l-type ca2+ channels
39
why is there a plateau at phase 2
calcium into the cell and K+ out of the cell balance each other out
40
what channels close at phase 3? what remains open
l type ca2+
k+ still open
41
what does a cardiac myocyte action potential depend on
extracellular calcium
We depend on extracellular calcium to trigger intracellular calcium release in the myocyte
▪ Every single “twitch” in the cardiac muscle cell has to be long enough to get enough calcium into the cell to trigger a useful (force-wise) contraction
▪ Long-lasting calcium increases mandate longer calcium influx and longer action potentials in the heart
42
what cannot occur in cardiac myocyte
TETANY
▪ Would be very difficult to “guarantee” that the myocytes relax (and then there’s no filling)
▪ The long action potential gives the cell time to start clearing calcium out of the cytosol prior to the next action potential
43
what is a calcium spark
When a single calcium VGC opens, it elicits a small amount of calcium release from the neighbouring ryanodine receptor on the SR
44
how to increase cytosolic calcium in a myocyte
summation of calcium sparks (and some ECF ca2+ entry)
calcium sparks is when 1 ca2+ VGC open tis elicits a small amount of ca2+ release from neighbouring ryanodien receptor s
45
how is calcium sequesterded in cardiac myocyte?
* SERCA – smooth endoplasmic reticulum calcium ATP-ase
* Sarcolemmal calcium ATP- ase
* Sodium-calcium exchanger
46
what does SERCA do
Pumps calcium into the SR,
47
what regulated SERCA activity of pumping ca2+ into the SR
regulated by a mediator known as phospholamban
▪ Phosphorylation of phospholamban ! increased SERCA activity
48
what does sodium calcium exchanger do
▪ Brings in 3 sodium and
extrudes one calcium
▪ Impact on membrane potential: depolarize and make more positive?
49
what does activation of SNS (beta 1 receptors do)
increase cAMP
leads to lots of phosphorlyation
50
increasing of cAMP from SNS leads to phosphorlayiton of
* Phosphorylation of phospholamban
* Phosphorylation of troponin
▪ Decreased calcium affinity
* Phosphorylation of the L-type calcium VGC
▪ Increased entry of calcium
▪ “fills” the SR more and increases the amount of calcium released with each spark
51
what impact does SNS activation have on cardiac myocytes
Increased cytosolic calcium release with each action potential
* Increased rate of relaxation after the action potential has ended
Net result – more forceful, “quick” contractions and a quicker transition to relaxation
52
how does SNS increase force of contraction
* Increased cytosolic calcium release with each action potential
▪ Engages more myosin heads --> greater force of contraction
53
how does SNS increase rate of relaxation after action potential has ended
Reduced troponin affinity --> “faster” release of calcium when calcium starts to drop --> faster relaxation
▪ Increased activity of the SERCA --> increased clearance of calcium into the SR
54
what 2 things does the force a cardiomyocyte generate with each systole depend on?
inotropy (contractility)
and
preload
55
what is ionotropy (contractility)? what factors increase it?
Amount of calcium available to bind to troponin – this is known as inotropy
* Factors that increase inotropy:
▪ Increased sympathetic nervous system
stimulation
▪ Increased heart rate (“loads” more calcium in the SR during relaxation)
▪ Things that increase SNS effectiveness – thyroid hormone, cortisol, etc.
56
what is preload
Optimal overlap between actin and myosin during diastole
* This is mostly determined by the state of ventricular filling – also known as preload
57
what is the optimal myocyte length for preload and to get best contraction
1.95-2.25um
58
what needs to generate more force atria or ventricles? how does this affect action potential?
ventricles (bc go to body) (atria just goes to ventricles)
atria:
▪ Systole and the action potential overall are shorter
▪ Local differences in ion channel expression
59
atria vs ventricles for action potentials
atria have:
Resting membrane potential (phase 4) of atria is slightly more depolarized than of ventricles due to reduce potassium
Lower plateau (phase 2) of atrial action potential due to lack of Ca2+ channels
60
which type of cells are automated
* Automated cell action potentials refer to the electrical activity in specialized heart cells, such as those in the sinoatrial (SA) node, atrioventricular (AV) node, and Purkinje fibers, which generate action potentials spontaneously.
61
what do automatic cells not need to depolarize? what does this make them?
external stimuli; pacemaker
These cells have the ability to depolarize automatically without external stimuli, allowing them to act as the heart's natural pacemakers, maintaining a rhythmic heartbeat.
62
automatic cells,,,
▪ They depolarize spontaneously
▪ The heart does not depend on the
nervous system to initiate contraction
* Many populations of cells have the ability to act as pacemakers in health
* Almost every cell can act as a pacemaker during severe cardiac disease (not a good idea)
63
what is the heart rate governed by
whatever automatic cells depolarize most frequently
▪ The action potentials then travel through the syncytium to all cardiomyocytes
64
what is special about phase 4 "resting membrane potential" in automatic cells
funny current; not stable
▪ Phase 4 is not stable, like it is in cardiomyocytes
▪ There is a weird channel that conducts sodium and a bit of potassium, and it is open during hyperpolarization and closes during depolarization
▪ Known as the funny current (mostly accounted for by gNa+i and a bit of the
gK+
▪ Potassium conductance also decreases near the end of phase 4
65
what happens in between action potentials in automatic cells
automatic cells spontaneously depolarize because they “leak” positive charge into the cell
66
RMP for automatic cells vs cardiomycotes
much more positive around -45mv compared to likee -84mv
67
phase 0-depolarization in automatic cells; what causes it?
l-type calcium channels (around -45 mV) and calcium influx
not the Na+ channels
68
How does activation of the parasympathetic NS change the characteristics of the automatic action potential?
1. decrease heart rate (negative chronotropic effect)
2. increase hyperpolarization (negative dromotropic effect)
3. reduce conduction velocity
69
How does activation of the parasympathetic NS change the characteristics of the automatic action potential?
* Increased K+ Conductance leads to hyperpolarization and a slower rate of depolarization.
* Decreased Ca2+ Influx slows down depolarization during phase 0.
* Increased Atrial Refractory Period extends the time between action potentials, further decreasing heart rate.
* These combined effects lead to
* a slower heart rate
* reduced cardiac output during parasympathetic activation
70
chronotropy
The rate of depolarization of automatic cells
71
positive ionotropy (speed up heart)
SNS increases the rate of depolarization and renders the RMP somewhat more positive
72
negative ionotropy
PNS decreases rate of spontaneous depolarization, increases the threshold for calcium VGC, and makes the RMP somewhat more negative
73
2 key features of automatic cells
1. unstable resting membrane potential
2. no plateau phase (phase 2)
74
unstable resting membrane potential in automatic cells
Unlike non-pacemaker cells, pacemaker cells do not have a stable resting membrane potential. Instead, their membrane potential gradually depolarizes during phase 4, leading to spontaneous action potentials
75
no plateau phase in automatic cells
The typical plateau (phase 2), seen in atrial and ventricular myocytes due to Ca2+ and K+ balance, is absent in automatic cells.
* Calcium-based depolarization: Phase 0 is dominated by Ca2+ influx, as opposed to the Na+ influx seen in atrial and ventricular myocytes, making the depolarization slower.
76
3 examples of automatic cells
SA node
AV node
purkinje fubres
77
what is the primary pacemaker of the heart
sinoatrial (SA) node
78
sinoatrial node
he primary pacemaker of the heart. The SA node sets the rhythm by spontaneously generating action potentials, which spread through the atria, causing them to contract.
79
atrioventricular node
Located between the atria and ventricles, the AV node can also generate action potentials but at a slower rate than SA node. It serves as a backup pacemaker and helps coordinate the contraction between the atria and ventricles.
80
purkinje fibers
While Purkinje fibers are mainly responsible for rapid conduction of action potentials through the ventricles, they can also act as pacemaker cells under certain conditions if the SA and AV nodes fail.
81
4 phases in an automatic cell
* Phase 4: Gradual depolarization due to funny Na+ current (I_f) and T-type Ca2+ influx.
* Phase 0: Rapid depolarization caused by L-type Ca2+ influx.
* Phase 3: Repolarization due to K+ efflux.
* Phase 1 and 2 are absent.
82
which phases are in automatic cells
phase 1 and 2
83
what is responsible for depolarization in phase 0 of automatic cells
L-type Ca2+ influx
84
what is a pacemaker cell
highly specialized cell with an intrinsic ability to depolarize rhythmically and initiate an action potential
Generate the rhythm for the entire heart
85
what are the bpm for the 3 pacemakerr cells
SA node: 60-100 bpm – the fastest pacemakers take the lead!
AV node: 40-60 bpm
Purkinje fibers: 20-40 bpm
86
is SA node fails (fastest pacemaker) what happens
If SA node fails (AP is not conducted to the AV node), the AV node can generate its own rhythm and so on
For example, in complete heart block – the impulses can’t be conducted from atria to the ventricle and the Purkinje fibers provide the action potential necessary to generate muscle contraction
87
SA and AV nodes have classical automatic action potentials; what is different about the purkinje fibres
very slowly “automatically depolarizing” phase 4
Otherwise, Purkinje fibres have identical action potentials to myocytes
88
when do purkinje fibers act as pacemakers
pathologic states
89
what happens when SA node pacemaker depolarized
When it depolarizes, AP spreads to AV node and across
both atria
90
what does the AV node do
asetof automatic cells that allow the AP to enter the AV bundle, but delay conduction
91
gap junctions in automatic cells create ___ resistance
Automatic and Purkinje fibres here have fewer gap junctions! higher resistance
92
what is the importance of the delay ins conduction at the AV node
▪ Gives the atria time to eject blood into the ventricle prior to
ventricular contraction
▪ As heart rate increases, the conduction through the AV node slows a little more (better filling)
93
what is the bundle of his
AV bundles
94
bundle of his (AV bundles) does what?
carry the AP along the septum (first part of the ventricle to depolarize)
95
where do purkinje fibres carry the AP to
carry the AP to the apex and then towards the base of the heart
96
conduction system
SA --> AV node --> bundle of his --> purkinje fibers --> apex --> base of heart
97
conduction pathway 5 steps
1. Impulse Generation: The SA node generates an action potential.
2. Atrial Contraction: The impulse spreads through the atrial muscle, causing atrial contraction.
3. AV Node Delay: The impulse reaches the AV node, where it is delayed, allowing the ventricles to fill.
4. Bundle of His: The impulse travels down the Bundle of His into the right and left bundle branches.
5. Purkinje Fibers: Finally, the impulse spreads through the Purkinje fibers, causing simultaneous contraction of the ventricles.
98
what does the fibrous skeletal in the heart help with
prevents direct conduction from atria to ventricles, isolating them and ensuring that the only electrical communication occurs through the AV node.
99
what are the critical junctions for electrical signals in the heart
The AV node and Bundle of His serve as critical junctions for electrical signals
* Left bundle branch further divided into anterior and posterior fascicles
* Right bundle branch has a single fascicle.
100
Bachmann's bundle allows for
rapid conduction from the right atrium to the left atrium, facilitating simultaneous atrial contraction.
101
ECGs to evaluate
▪ Arrhythmias
▪ Estimation of abnormal cardiac size ▪ Electrolyte abnormalities
▪ Cardiac ischemia
▪ Sometimes useful findings in:
* Pericarditis
* Pulmonary emboli
102
what do ECGS measure
electrical events
ECGs only evaluate electrical events in large numbers of cells – they can only “see” electrical events in myocytes
▪ They also record the changes in extracellular potential (not intracellular), so the waveforms are actually the inverse of what is happening in the myocyte
103
what do ECGS measure
measure electrical differences across the heart
▪ If the whole heart is depolarized, the ECG tracing is at baseline
▪ If the whole heart is repolarized, the ECG tracing is at baseline
* When there is a difference in electrical state in 2 separate areas of the heart, there is a “wave”
104
what does the height of a wave in an ECG correspond to
how large the electrical potential difference is across two separate parts of the heart
105
where are ECG leads place on the body to give a 3D view
* Coronal view (left and right arms, left leg)
* Cross-sectional view (precordial leads)
106
what is x and y axis of ECG diagram to measure electrical changes across the heart over time
* Time – x-axis, in seconds
* Electrical potential changes – voltage in mV, y-axis
107
on an ECG graph what is the height and width of a little box and big box
* “little box” – 0.1 mV high, and 0.04 seconds wide
* Each “big box” is 0.5 mV by 0.2 second
108
a wave in an ECG
A “wave” is a deflection from baseline in across the heart voltage
▪ Examples of waves:
* P waves
* QRS waves * T waves
109
what is an interval in an ECG
An “interval” is a “space” between and often including waves
▪ Examples of intervals:
* P-R interval
* QRS interval * QT interval
110
p wave
atrial depolarization initiated by the SA node
111
PR interval
time it takes for action potential to travel from SA node to the AV node
Delay at the AV node allowing for ventricular filling.
112
QRS complex
ventricular depolarization
rapid depolarization of the ventricles via the conduction pathway (Bundle of His and Purkinje fibers).
113
ST segment
The period when the ventricles are fully depolarized and before they repolarize
114
T wave
Ventricular repolarization returning the heart to its resting state
115
QT interval
Total time for ventricular depolarization and repolarization
116
atrial action potential consist of what on the ECG
1. p wave
2. PR interval
117
ventricular action potential consist of what on the ECG
1. QRS complex
2. t wave
3. QT interval
118
atrail action potential
* P Wave: Corresponds to the rapid depolarization (Phase 0) of the atria.
* PR Interval: Reflects the duration of atrial depolarization and conduction through the AV node
119
ventricular action potential
* QRS Complex: Corresponds to the rapid depolarization (Phase 0) of the ventricles.
* T Wave: Corresponds to the repolarization (Phase 3) of the ventricles.
* QT Interval: Represents the total time for ventricular depolarization and repolarization.
120
what do cardiac myocytes have a lot of
mitochondria
121
what do the mitochondria in cardiac myocutes want as their metabolism dn fuel source>
▪ Depend on oxidative metabolism – preferential use
of fats
▪ Very little glycogen storage – use of circulating FFAs
▪ Energy efficient, high-energy ATP source
▪ Anaerobic metabolism provides very little ATP – therefore myocytes require constant blood flow (“stunning” and death within minutes)
122
purkinje fibers and automatic cells have ____ oxygen requirement compared to cardiac myocytes because ____
lower; no sarcomeres
123
heart failure
* Contractility is significantly impaired resulting in reduced ejection fraction (how much is pumped out versus how much remains in the ventricle)
124
cardiac arrest
* Heart suddenly and unexpectedly stops pumping, often caused by ventricular arrhythmia’s, such as ventricular fibrillation or ventricular tachycardia
125
angina
* Pain brought on by ischemia, that doesn’t result in permanent heart damage
126
tachyarrhythmia
* Abnormal heart rhythm (arrhythmia) with a heartbeat of >100 beats per minute (tachycardia)
127
