Cardiac action potentials Flashcards
Describe the process which generates the resting membrane potential of cardiac cells
The cell membrane of myocardial cells is mostly permeable to K+ ions. So the cardiac resting membrane potential of ~ -90mV is largely due to the K+ equilibrium potential of -80mv (see membranes and receptor module). K+ ions move down their concentration gradient, from the inside to the outside of the cell, taking their positive charge with them.
Draw and explain the membrane permeability changes in: ventricular myocytes
o In diastole, the resting membrane potential of cardiac cells is close to the equilibrium potential of K+
o Initial depolarisation due to spread of electrical activity from pacemaker cells. Once threshold has been reached, fast voltage gated sodium channels are opened, causing depolarisation towards Na+’s equilibrium potential
o Following the rapid depolarisation, a brief repolarisation caused by the outward flow of K+ returns the membrane potential to ~0.
o Na+ channels deactivate, but the depolarisation causes the opening of voltage gated Ca2+ channels, which take longer to activate, keeping the membrane depolarised
o Influx of Ca2+ causes the release of further Ca2+ from cellular stores, causing contraction
o After ~250ms, Ca2+ channels close.
o Efflux of K+ returns membrane potential to resting
Draw and explain the membrane permeability changes in: pacemaker cells
o The spontaneous gradual depolarisation of pacemaker cells, the pacemaker or ‘funny’ current (If) is carried by Na+ ions through slow Na+ channels that open during the repolarisation of the cell as the potential approaches its most –‘ve values.
o Once the cell reaches its threshold voltage due to the If, Ca2+ channels open, giving a relatively slow depolarisation. This is due to the deactivation of the fast Na+ channels.
o Once Ca2+ channels close, the cell repolarises due to K+ efflux.
Describe the membrane potential changes in pacemaker cells associated with increases/ decreases in heart rate
Increasing Heart Rate
The interval between beats depends on how fast the pacemaker potential depolarises. The interval is shortened by the action of the Sympathetic nervous system on the SAN. Noradrenaline (β1 Receptor) speeds up the heart rate by making the pacemaker potential steeper.
Decreasing Heart Rate
The interval between pacemaker potentials is lengthened by the action of the Parasympathetic nervous system on the SAN. Acetylcholine (M2 Receptor) slows the heart rate by making the pacemaker potential shallower.
Describe the cellular mechanisms controlling heart rate
Baroreceptors:
Baroreceptors, located in the arch of the aorta and the carotid sinus have a role in controlling Heart rate. When arterial blood pressure is high, the aorta/carotid arteries are stretched, activating the stretch sensitive baroreceptors.
The baroreceptors pass the information to the medulla, which in turn causes parasympathetic innervation of the SAN.
Parasympathetic innervation causes the pacemaker potential to become shallower, slowing the heart rate.
Describe the types of drugs used to treat patients with common cardiovascular disorders
Cardiovascular drugs are used to treat: - Arrhythmias - Heart Failure - Angina - Hypertension - Risk of thrombus formation Cardiovascular drugs can alter: - The rate and rhythm of the heart - The force of myocardial contraction - Peripheral resistance and blood flow - Blood volume
Explain the effects of ectopic pacemaker activity
Ectopic Pacemaker activity
- Damaged area of myocardium because depolarised and spontaneously active.
- Latent pacemaker region activated due to ischaemia
- Dominate over SA node
Explain arrhythmia and after-depolarisation effects
- Abnormal depolarisations following the action potential
- Thought to be caused by high intracellular Ca2+
- Longer AP leads to longer QT interval
What is a re-entry loop?
- Conduction delay
- Normal spread of excitation disrupted due to damaged area
- Incomplete conduction damage (uni-directional block)
What are the 4 basic classes of anti arrhythmic drugs?
There are 4 basic classes of anti-arrhythmic drugs:
I. Drugs that block voltage gated Na+ channels
II. Antagonists of -adrenoceptors
III. Drugs that block K+ channels
IV. Drugs that block Ca2+channels
Define the term inotropic drug and the circumstances under which these drugs can be used
Inotropic drugs are drugs that affect the force of contraction of the heart.
Negatively inotropic drugs are used in circumstances where it is beneficial to reduce the workload of the heart, for example after a myocardial infarction. This reduces the O2 requirement of the heart and limits further damage. -blockers are examples of negative inotropic drugs.
Positive Inotropic drugs are used in circumstances where the heart needs to beat more strongly, for example cardiogenic shock or acute but reversible heart failure (eg following cardiac surgery). -adrenoceptor agonist, e.g. dobutamine are examples of positive inotropic drugs.
Describe how drugs can be used in the treatment of heart failure
ACE-inhibitors and diuretics have an important role in the treatment of chronic heart failure. ACE-inhibitors prevent the formation of the vasoconstrictor angiotensin II, thus promoting vasodilation of arterioles and venous dilation. This decreases both afterload and preload to the heart.
ACE-inhibitors also have a diuretic action since angiotensin II promotes aldosterone release from the adrenal cortex (zona glomerulosa). Aldosterone causes Na+ and water retention, increasing blood volume – so reducing it decreases blood volume and decreases pre-load to the heart.
Describe how drugs can be used in the treatment of angina
Angina occurs when O2 supply to the heart does not meet its need. Ischemia of the heart tissue leads to chest pain, usually on exertion and relieved by rest. It is due to narrowing of the coronary arteries (atheromatous disease)
Angina is treated by reducing the work load of the heart, with -blockers, Ca2+ channel blockers, and organic nitrates. Organic nitrates and Ca2+ channel blockers also improve Blood supply to the heart.
outline the action of organic nitrates
Action of Organic Nitrates
The reaction of organic nitrates with thiols (-SH groups) in vascular smooth muscle causes NO2- to be released. NO2- is reduced to NO, which is a powerful vasodilator. NO activates guanylate cyclase, increasing cGMP and lowering intracellular Ca2+ to cause relaxation of vascular smooth muscle.
Primary Action
Acts on the venous system as a venodilator (Note – VENOdilator), lowering central venous pressure and preload. The heart fills less; therefore force of contraction is reduced (Starling’s Law).
Secondary Action
Acts on the coronary arteries, improving O2 delivery to the ischaemic myocardium.
In which cardiac conditions is thrombus formation a risk? explain
Certain heart conditions, such as atrial fibrillation and valve disease carry an increased risk of thrombus formation. Anti-thrombotic drugs such as warfarin may be used in these cases. The anti-platelet drug aspirin is used following MI or in coronary artery disease where there is a risk of MI to reduce the risk of platelet rich arterial clots forming.
