Molecular Events in CVS

Question 0

Outline the molecular events in the SAN action potential.

Answer 0

1. Gradual, spontaneous depolarisation due to ionic flux of Na+ (funny current) activated by HCN channels (hyperpolarisation)
2. HCN channels inactivated (Na+ does NOT contribute to the upstroke)
3. Opening of voltage-gated Ca2+ channels (upstroke)
4. Opening of voltage-gated K+ channels & inactivation of Ca2+ channels (downstroke)
5. Resting membrane potential reached (~-60mv?) (unstable; too positive to allow fast Na+ channels to be activated)

Question 1

Outline the molecular events of the ventricular action potential.

Answer 1

1. Opening of fast voltage-gated Na+ channels —–> influx of Na+ ——> depolarisation ——–> threshold potential reached ——> self-sustaining inward Na+ current
2. Opening of transient voltage-gated K+ channels ——> efflux of K+ ———> repolarisation
3. Opening of L-type voltage-gated Ca2+ channels —–> influx of Ca2+ (balanced by delayed rectifier K+ channel efflux - plateaus)
4. Ca2+ channels inactivate & efflux of K+ through voltage-gated channels repolarises the cell
5. Resting membrane potential (~90mV) restored

Question 2

What proportion of calcium is released by the L-type Ca2+ channels and the ryanodine receptor respectively?

Answer 2

L-type Ca2+ channels = ~10-25%

Ryanodine (calcium-induced calcium release) = ~75-90%

Question 3

How does increased [Ca2+]i cause muscle contraction, apart from binding to troponin to reveal the binding site on tropomyosin? (check)

Answer 3

Calcium binds to calmodulin (which type of muscle? smooth?)

Calcium-calmodulin binds to myosin light chain kinase (MLCK) (regulatory)

Ca2+-MLCK activates myosin II head

Myosin II head activates myosin light chain phosphatase (MLCP) which allows muscle contraction (MLCP is constitutively active)

note: PKA inhibits MLCK, PKC inhibits MLCP

Question 4

What is the parasympathetic control of the heart?

Answer 4

Vagus nerve synapses with postganglionic on epicardial surface & within walls of heart at SAN & AVN

ACh acts on M2-receptors (Gi) (by subunit increases K+ conductance)

Negative chronotropy & reduced AVN conduction velocity

Question 5

What is the sympathetic control of the heart?

Answer 5

Postganglionic fibres of sympathetic trunk innervates SAN, AVN, & myocardium.

Noradrenaline acts on beta-1-adrenoceptors (Gs?)

Positive chrontropy & inotropy