Revision 7: Cellular and Molecular Events in the Heart

Question 1

factors determining resting membrane potential of cardiac cells

Answer 1

K⁺ has a higher conc. inside the cell, Na⁺ has a higher conc. outside the cells

E_k=-90mV

mostly permeable to K⁺, so has a resting membrane potential close to -90mV

Question 2

changing membrane potential of ventricular cells

Answer 2

0 -> initial depolarisation from spread of electrical activity from p.maker cells reaching threshold potential, fast Na⁺ VGCPs open and depol. towards E_Na

1 -> brief repol. by outward flow of K⁺ ions to ~ 0mV

2 -> Na⁺ VGCPs deactivate, Ca²⁺ VGCPs open which take longe to activate and keeps the membrane depolarised, release of further Ca²⁺ from intracellular stores leading to contraction, after ~250ms these channels shut

3 -> efflux of K⁺ repolarises

4 -> diastole, membrane potential ~ E_K = -90mV

Question 3

changing membrane potential of pacemaker cells

Answer 3

as the mV is always above -90mV, fast Na⁺ VGCPs are permanently inactivated

spontaneous depolarisation of the cells caused by p.maker/funny current (I_f), made by Na⁺ in slow Na⁺ VGCPs (these open during repol. as the most -ve mV is reached)

cell reaches threshold due to I_f, Ca²⁺ VGCPs open, slow depol. due to closure of fast Na⁺ channels

once Ca²⁺ VGCPs close the cell repol.s due to K⁺ efflux

Question 4

cellular mechanisms controlling HR

Answer 4

HR depends on interval between beats -> how fast the I_f depolarises

inc. HR -> SyNS on SAN -> NAdr on beta-1 -> p.maker potential steepens
dec. HR -> PSNS on SAN -> ACh on M₂ -> pacemaker potential shallower

baroreceptors in aortic arch and carotid sinus react to press: inc press -> aorta/carotid arteries stretched -> M.O. -> PSNS

Question 5

what can CVS drugs be used to treat and alter?

Answer 5

treats: arrhythmias, heart failures, angina, hypertension, thrombus formation prevention
alter: rate and rhythm of heart, force of myocardial contraction, blood vol., peripheral resistance and blood flow

Question 6

Causes of arrythmias

Answer 6

Ectopic p.maker activity: damaged area of muscle is depol. and becomes spont. active, latent p.maker region is activated by ischaemia and dominates over the SAN

After-depolarisations: abnormal depol. following an AP, thought to be caused by high [Ca²⁺]_in, longer AP -> longer QT interval

Re-entry Loop: normal spread of depol. disrupted by damaged area, incomplete conduction damage (unidirectional) can cause circular route of depol.s that never ends, several RELs in atria lead to an atrial fibrillation

Question 7

anti-arrhythmic drugs

Answer 7

I: Block Na⁺ VGCs: eg local anaesthetic lidocaine, open/inactivated channels are blocked, dissociates rapidly in tim efor next AP so prevents after-depol.s

II: Beta-2 adrenoceptor antagonists: eg propranolol, atenolol, prevents SyNS acting so dec. chronotropy, inotropy, used after an MI to dec. O₂ demand

III: Block K⁺ channels: inc. Abs. Ref. Per. to prevent another AP acting too soon, rarely used as they can be pro-arrthymic

IV: Block Ca²⁺ channels: dec. slope of p.maker AP at SAN, dec. AVN conductance and inotropy, some coronary and peripheral vasodilatation

Adenosine: acts on adenosine A1 (NOT alpha-1) receptors at AVN (GPCRs -> inh.s Ad. Cyc.), enhances K+ conductance, hyperpol.s cells of conductance tiss., ‘resets’ heart

Question 8

inotropic drugs uses

Answer 8

+ve: eg after cardiogenic shock, acute reversible heart failure, Beta-adrenoceptor agonists eg dobutamine

-ve: eg after MI, reduces O₂ workload, limits further damage, beta-blockers

Question 9

drugs used in treatment of heart failure

Answer 9

ACE (Angiotensin-Converting Enz.) inhibitors and diuretics

ACE inhibitors: prevent formation of Angiotensin II, a vasoconstrictor, reduces pre and after load

also has diuretic action, as angiotensin promotes aldosterone release

-> reducing this means more Na⁺ and water loss -> reduced blood vol. and pre-load

Question 10

cause and treatment of thrombus and treatment of hypertension

Answer 10

thrombus eg atrial fibrillation, valve problems

treated by anti-thrombotic warfarin, as well as anti-platelet aspirin after MI/CAD

hypertension: drugs reduce CO a/o periph. resistance

eg ACE inhibitors, diuretics, adrenoceptor blockers, Ca²⁺ channel blockers

Question 11

treatment of angina

Answer 11

angina occurs by hypoxia to heart, drugs act to reduce work load eg beta blockers, Ca2+ channel blockers, organic nitrates

Org. Nit.s: react with thiols (-SH) to form NO₂^- in SMCs, reduced to NO, powerful vasodilator -> activates guanylate cyclase -> inc. cGMP and dec. [Ca²⁺]_in -> relaxation of vasc. SMCs

• 1^o action: VENOdilator, dec. ven. press., after and pre load
• 2^o action: coronary arteries, improving O₂ delivery to isch. myocardium