Cardiac Contraction Flashcards
(68 cards)
1
Q
What are the effects of positive inotropic agents?
A
Increase myocardial contractility by increasing intracellular [Ca2+]
2
Q
What are dopamine and dobutamine usually used for?
A
Acute heart failure
3
Q
Outline a possible mechanism of action for dopamine
A
- stimulate β-adrenoreceptors on the heart
- weak stimulation of other adrenoreceptors found in body - so main target is heart
- similar action to noradrenaline
4
Q
When is glucagon used clinically?
A
- Treat acute heart failure
- Glucagon is used if patient uses beta blockers
5
Q
Outline a mechanism of action for glucagon
A
- acts on the heart
- stimulates Gαs-linked GPCRs ∴increased conversion of ATP to cAMP ∴ increased activation of PKA
6
Q
What is the purpose of PDE3?
A
TYPE 3 PHOSPHODIESTERASE
- Converts cAMP to ATP ∴ reduced concentration of cAMP ∴ reduced activation of PKA ∴ reduced contractility
7
Q
Outline the mechanism of action of Amrinone
A
- Inhibits PDE3
- Prevents reduction in cAMP concentration ∴ increased activation of PKA ∴ greater phosphorylation of calcium ion channels ∴ greater contractility
8
Q
What are cardiac glycosides - give an example.
A
- Increase output force of contraction of heart whilst decreasing rate of contraction through inhibition of the sodium-potassium ATPase exchanger
- Example - digoxin
9
Q
Outline the importance of the sodium-potassium ATPase exchanger.
A
- Draws on energy from ATP hydrolysis
- For every ATP molecule consumed, 3 sodium ions are exported and 2 potassium ions are imported (maintains sodium ion gradient)
10
Q
How does the sodium-calcium ion exchanger use the sodium ion gradient?
A
- Gradient is used to remove calcium ions from inside the cell
11
Q
Given that digoxin inhibits the sodium-potassium ATPase exchanger, suggest how the sodium-calcium exchanger is affected by digoxin.
A
Increased intracellular [Na+] ∴ reduced gradient and therefore reduced entry of sodium ions through sodium-calcium ion exchanger
12
Q
How are the calcium ion concentrations affected by digoxin?
A
- Reduced influx of sodium ions through sodium-calcium ion exchanger
- Increased intracellular [Ca2+] ∴ increased cardiac contraction
- Increased [Ca2+] within SR stores ∴ greater CICR ∴ greater force of contraction
13
Q
Where are the β-adrenergic receptors found?
A
- Contractile cells of the heart
14
Q
Briefly outline the structure of the β-adrenergic receptors.
A
- Made up of a single protein
- 7 transmembrane domains
- Linked to a Gαs subunit
15
Q
Outline the mechanism of action of a beta adrenergic receptor
A
- Gαs subunit binds to and stimulates adenylate cyclase
- Increased conversion of ATP to cAMP
- Increased activation of PKA ∴ calcium ion channels are phosphorylated
- Increased intracellular [Ca2+] ∴ greater CICR ∴ greater binding to troponin C
- Greater actin-myosin interactions ∴ greater pacemaker potentials - increased ionotropy and contractility
16
Q
How does sympathetic stimulation influence the activity of voltage-gated calcium ion channels?
A
- Increased activity ∴ increased calcium ion influx ∴ increased intracellular [Ca2+]
- Greater amplitude in plateau phase
- Greater depolarisation ∴ greater contraction
17
Q
How does sympathetic stimulation influence sarcoplasmic reticulum Ca2+-ATPase activity?
A
- Increased activity
- Increased uptake of calcium ions into SR stores ∴ faster decrease in calcium ion concentration ∴ faster relaxation
18
Q
How does sympathetic stimulation influence potassium ion channel activity?
A
- PKA causes these channels to open
- Faster repolarisation ∴ shorter but faster action potentials but with greater amplitudes in given time∴ greater heart rate
19
Q
How does sympathetic stimulation influence diastolic time?
A
- Time stays constant
- Still needed for filling of chambers with heart and coronary perfusion
20
Q
Name two ways in which pharmaceuticals can influence cardiac output
A
- Increase in activity of voltage-gated calcium ion channels ∴ increase intracellular [Ca2+] e.g noradrenaline
- Reduced expulsion of calcium from cytoplasm ∴ high intracellular [Ca2+] is maintained for longer e.g cardiac glycosides
21
Q
What is the typical result of increasing [Ca2+]?
A
- Harder/faster contraction
- Greater cardiac output
22
Q
What are the typical effects of calcium blockers and beta blockers?
A
- Reduced intracellular [Ca2+]
- Slower contraction
- Reduced cardiac output
23
Q
RELAXATION OF CARDIAC MUSCLE - What occurs to the voltage-gated sodium and potassium ion channels?
A
- Voltage-gated sodium ion channels close
- Voltage-gated potassium ion channels open
- Repolarisation occurs
24
Q
RELAXATION OF CARDIAC MUSCLE - What occurs after repolarisation of the action potential?
A
- Repolarisation of the T-tubules
- Closure of the voltage-gated calcium ion channels ∴ reduced influx of calcium ions
- No CICR from the SR
25
RELAXATION OF CARDIAC MUSCLE - How does the muscle cells respond to the high calcium ion concentration in the cell?
- Sodium-calcium exchanger removes calcium ions from the cell in exchange for sodium ions
- Most calcium ions are taken back up into the SR using the sarcoplasmic Ca2+ ATPase (requiring energy)
- Some calcium ions are taken up by the mitochondria
26
Define myocardium
The muscles found within the central layer of the walls of the heart
27
What specialised cells is the myocardium made up of?
Cardiomyocytes
28
Outline the difference between inotropy and Starling's Law.
Starling's Law is intrinsic - inotropy is extrinsic
- Starling's Law is linked to an increase in volume due to stretch ∴ not linked to a rise in [Ca2+]
29
What does a typical Starling curve tell about filling pressure.
Filling pressure on x-axis
- As pressure increases so does the cardiac output
- Greater initial stretch ∴ greater force of contraction up to a certain point - beyond this point, plateaus
30
How does the use of a positive inotropic agent influence a Starling curve?
- Curve shifted upwards so Starling's law still applies
- Force of contraction increases
31
Outline the first step of cardiac contraction.
- Action potential initiated at SAN and passed through adjacent cardiomyocytes through gap junctions
- Activates VGCCs in the T-tubules causing Ca2+ influx into the cardiomyocyte
- Calcium ions bind to troponin-C in the sarcomere
- Binding causes conformation of the tropomyosin complex ∴ actin binding sites are exposed
32
Outline the second and third steps of cardiac contraction
- Myosin in high energy form has ADP+phosphate
- Binds to exposed actin binding site, causing cross bridge to be formed ∴ phosphate released
- Myosin changes conformation and releases ADP ∴ actin filaments pulled towards centre of sarcomere (i.e powerstroke) . Myosin left in low energy configuration
33
Outline the fourth and fifth steps of cardiac contraction
- Myosin remains bound to actin until binding of ATP causes release from actin
- ATP hydrolysed to ADP and inorganic phosphate - myosin brought back to high energy form. Head is 'cocked' - prepared for another power stroke
- Cycle repeats along as calcium ions are present and actin binding sites remain exposed
34
Outline the final step of cardiac contraction
- Intracellular Ca2+ removed from SR actively ∴ decrease in [Ca2+]
- Troponin complex brought back into inhibiting position ∴ myosin can no longer bind
- Actin filaments return to original position ∴ muscle relaxes
35
What does troponin regulate?
Conformation of tropomyosin
36
What are the three subunits that troponin is made up of?
Troponin T
Troponin I
Troponin C
37
What does Troponin T bind to?
Tropomyosin
38
What does Troponin I bind to?
Actin filaments
39
What does Troponin C bind to?
Calcium ions
40
Describe the original conformation of tropomyosin (i.e when no calcium ions bound to troponin C)?
- Troponin I brought to active site and binds to actin filaments
- Prevents binding of myosin to actin
41
What is the clinical significance of the isoforms of Troponin I and Troponin T?
- Released into blood following damage to myocardium e.g following myocardial infarction
- Used to diagnose MI/ differentiate it from angina
42
What is cardiac contraction dependent on?
Increase in intracellular [Ca2+]
43
What are the striations in cardiac muscle a result of?
Z-lines
44
What do Z-lines mark?
Junction of actin filaments in adjacent sarcomeres
45
What does the relative movement of actin and myosin filaments cause?
- Z-lines brought closer together
- Muscle fibres shortened during contraction
46
What does calcium ions activate in smooth muscle?
Myosin light chain kinase (NOT TROPONIN)
47
What is the sarcoplasmic reticulum?
Membrane bound structure in muscle cells that stores calcium ions
48
What is the T-tubule system?
Invaginations in the sarcolemma - pass deep into the cardiac muscle cells
49
How do action potentials cause local rising in intracellular [Ca2+] through VGCCs?
- Wave of depolarisation - during action potentials - depolarises T-tubules ∴ activates VGCCs causing calcium influx
49
How do action potentials cause local rising in intracellular [Ca2+] through ryanodine receptors?
- Some calcium ions activate ryanodine receptors found in close proximity to ion channels
- Causes intracellular calcium release from SR.
- Local [Ca2+] rises ∴ CICR occurs
50
Why are the T-tubules and RyRs found near the sarcomeres?
Allows coordinated link between electrical activity and contraction
51
Outline how cardiac action potentials spread from cell to cell
Passes through gap junction-rich intercalated discs
52
What does the passage through intercalated discs allow the action potential to do?
Induce depolarisation in adjacent cells
- Allows spread of wave of depolarisation across the heart
53
What ion type facilitate the spreading of cardiac action potentials?
Na+
54
Outline a potential diagram fora cardiac action potential
SEE SLIDES
55
Outline what occurs during Phase 0 of the cardiac action potential
- Initial depolarisation triggers opening of sodium ion channels ∴ influx of sodium ions
- Membrane potential becomes more positive
56
Outline what occurs during Phase 1 of the cardiac action potential
- VGCCs open ∴ influx of calcium ions
- Initial dépolarisation due to action of sodium-potassium exchanger
57
Outline what occurs during Phase 2 of the cardiac action potential
- Plateau phase - calcium influx and CICR from intracellular stores ∴ increase in intracellular [Ca2+]
- Force of contraction will be proportional to intracellular [Ca2+]
58
Outline what occurs during Phase 3 of the cardiac action potential
- Repolarisation - voltage gated potassium ion channels open and VGCCs close ∴ muscle relaxation
- Membrane potential becomes less positive ∴ reaches stable resting potential
59
TRUE or FALSE - Calcium rise is part of an all or nothing response during contraction
WRONG
- Contraction is concentration-dependent
- Depending on how high [Ca2+] is, there can be greater forces of contraction
60
What is the normal cytosolic calcium concentration during resting phase?
0.1 μM
61
During normal contraction, what is the usual calcium concentration?
1 μM
62
During strong exercise/fight or flight responses, what is the usual calcium concentration?
10 μM
63
What do the intercalated discs contain?
Gap junctions
64
What is the purpose of gap junctions during contraction?
Allows wave of depolarisation to spread from one cell to next
65
What are the myofibrils made up of?
Sarcomeres
66
How do the myofibrils cause contraction?
They shorten
67
How do sarcomeres cause contraction?
Relative movement of actin and myosin filaments towards each other
