Cardiac Contraction Flashcards
What are the intracellular concentrations of Ca2+ during normal diastole and systole?
Diastole - [Ca2+]i = 100 nM
Systole - [Ca2+]i = 1 uM
When systolic contraction is greatest, such as in exercise,[Ca2+]i rises to approximately 10 uM. Explain why this causes an increased force of contraction compared to the heart at rest.
Cell shortening is normally sub-maximal. Up to 10 uM, increasing [Ca2+]i leads to a proportional increase in cell shortening and therefore an increase in force of contraction.
Cell shortening occurs during which phase of the atrioventricular action potential?
Phase 2 - the plateau phase - Ca2+ influx, K+ efflux.
Cardiomyocyte relaxation occurs during which phase of the atrioventricular action potential?
Repolarisation - K+ efflux, Ca2+ signal reduced.
What are the main two mechanisms that contribute to the rise in [Ca2+]i that leads to contraction?
- Ca2+ influx through VGCCs during plateau phase.
- Calcium-induced calcium release (CICR) - Ca2+ binds to ryanodine receptors on sarcoplasmic reticulum, triggering Ca2+ release into cytosol.
Describe the events leading from depolarisation to a rise in [Ca2+]i to contraction.
- Na+ influx depolarises T-tubules - activation of VGCCs, Ca2+ influx.
- Ca2+ binds to RyR on SR, causing CICR.
- Ca2+ binds to troponin, displacing troponin-tropomyosin complex and exposing active sites on actin.
- Myosin heads bind to active sites on actin - cross-bridge formation.
- Myosin head ATPase hydrolyses ATP to ADP and Pi, providing energy for power stroke.
- Filaments slide.
At the sub-cellular level, why does a rise in [Ca2+]i lead to greater contractility?
Increased Ca2+ > more actin active sites exposed > increased cross-bridge formation > increased contractility.
How does Ca2+ expose the active sites on actin?
Ca2+ binds to TnC site on troponin > conformational change causes TnI and TnT to move, exposing active sites on actin.
TnI and TnT are important blood plasma markers for what?
TnI and TnT in plasma indicate cardiac cell death following MI.
Describe the events leading from repolarisation to a decrease in [Ca2+]i to relaxation.
- K+ efflux repolarises T-tubules - closure of VGCCs.
- No Ca2+ influx - no CICR.
- Extrusion of Ca2+ from cell by Na+/Ca2+ exchanger (NCX).
- Ca2+ uptake into SR via SR Ca2+-ATPase (SERCA).
- Ca2+ uptake into mitochondria.
- Reduced [Ca2+]i, myosin head ATPase activity.
- Prevention of contraction mechanism.
What is the difference between inotropy and Starling’s law?
Inotropy is increased contractility due to increased [Ca2+]i, controlled extrinsically. Starling’s law describes how the intrinsic stretch of the heart influences stroke volume. Changes in inotropy shift the ventricular function curve (Starling curve) vertically.
What are the two main classes of positive inotropic drugs and what do they do?
All increase [Ca2+]i:
- Sympathomimetics - increase VGCC activity.
- Cardiac glycosides - reduce Ca2+ extrusion.
How does the sympathetic nervous system regulate contractility?
Postganglionic sympathetic fibres release NA, which acts on beta-1 receptors to increase contractility.
Stimulation of beta-1 receptors induces an increase in contractility. Explain how.
- NA acts on beta-1 receptors, causing activation of the Gs pathway.
- Adenylate cyclase is activated, which converts ATP to cAMP.
- Increased cAMP levels lead to increased activation of PKA.
- Activated PKA phosphorylates VGCCs, increasing conduction of Ca2+.
- Greater Ca2+ influx and CICR leads to greater [Ca2+]i and therefore greater contractility.
Name the 4 main sympathetic effects on the heart.
- Positive inotropic effect - increased contractility.
- Positive chonotropic effect - increased heart rate.
- Positive dromotropic effect - increased conduction through AV node.
- Positive lusitropic effect - increased rate of relaxation - K+ channels, SERCA.
