11-Drugs and the Heart

Question 1

Explain EC coupling in cardiac muscle

Answer 1

AP propagates along myofibril and T-tubule Depolarisation opens VGCCs -> Ca2+ influx Ca2+ causes calcium-induced Ca2+ release via RyR on SR, initiates contraction via troponin and causes further depolarisation

Question 2

What is the ß-adrenoceptor linked to?

Answer 2

Adenylate cyclase

Question 3

How does the ß-adrenoceptor affect the heart?

Answer 3

Linked to adenylate cyclase -> increase cAMP, increased PKA, phosphorylates phospholamban, activating SERCA and increasing SR Ca2+ store so subsequent beats have greater contractility

Question 4

Explain the SA node pacemaker potential

Answer 4

Phase 4 - K+ efflux and slow Na+ entry

Initial depolarisation is due to Na+ FUNNY current opening at negative membrane potential (-60 - -50mV) allowing slow Na+ influx

This opens T-type and L-type Ca2+ channels - rapid depolarisation (Phase 0)

Repolarisation occurs from K+ and Ca2+ efflux (Phase 3)

When cell gets back down to negative potential, automatic depolarisation due to funny current again

Question 5

How does ß-adrenoceptor activation change the pacemaker potential?

Answer 5

ß-adrenoceptor linked to adenylate cyclase, more cAMP, PKA phosphorylates PLN, activating SRCA, more Ca2+ influx so more vertical stage 4 depolarisation and prolongs K+ efflux

Parasympathetic = opposite

Question 6

How do cardiac glycosides work?

Answer 6

Positive inotropy but negative chronotropic effect

Blocks both the Na/K ATPase and Na/Ca2+ ATPase (3 Ca out for every Na+ in)

Na+ builds up inside cell, more Na+ can’t be pumped in in exchange for Ca2+ out, so Ca2+ builds up in cell

Increased contractility due to Ca2+, but reduced heart rate

Question 7

Describe the function of Ca2+ channel blockers

Answer 7

1) Rate-slowing (verapilmil) - cardiac + smooth muscle effects

2)Non-rate slowing (dihydropyridines) - cardiac only
But cause vasodilatation, fall in BP and reflex tachycardia

Both decrease Ica current, so prolongs time for each pacemaker depolarisation

Question 8

How do organic nitrates work?

Answer 8

NO stimulates guanylate cyclase, more cGMP, more PKG which inhibits SR Ca2+ channels, less Ca2+ = smooth muscle relaxation

Also more K+ efflux

Increase coronary blood flow, vasodilatation decreases afterload and venodilatation decreases preload