Question

Describe the sinoatrial node (SA node) membrane potential and action potential.  Describe how these would be affected by: 1) atropine, 2) norepinephrine, and 3) acetylcholine

Answer 1

Sinotrial node is a specialised myo-cardial structure that initiate the electrical pulses to stimulate contraction and is found in the atrial wall at the junction of superior caval vein and right atrium. SA node send out regular electrical impulses from the top chamber which is known as atrium. Causing it to contract and pump blood into bottom chamber which is known ventricle. The electrical impulse is then conducted to the ventricle through a form of junction box called AV Node.Cells within the sinoatrial (SA) node are the primary pacemaker site within the heart. These cells are characterized as having no true resting potential, but instead generate regular, spontaneous action potentials. Unlike non-pacemaker action potentials in the heart, and most other cells that elicit action potentials (e.g., nerve cells, muscle cells), the depolarizing current is carried into the cell primarily by relatively slow Ca++ currents instead of by fast Na+ currents. There are, in fact, no fast Na+ channels and currents operating in SA nodal cells. This results in slower action potentials in terms of how rapidly they depolarize. Therefore, these pacemaker action potentials are sometimes referred to as "slow response" action potentials.SA nodal action potentials are divided into three phases. Phase 4 is the spontaneous depolarization (pacemaker potential) that triggers the action potential once the membrane potential reaches threshold between -40 and -30 mV). Phase 0 is the depolarization phase of the action potential. This is followed by phase 3 repolarization. Once the cell is completely repolarized at about -60 mV, the cycle is spontaneously repeated.

The changes in membrane potential during the different phases are brought about by changes in the movement of ions (principally Ca++ and K+, and to a lesser extent Na+) across the membrane through ion channels that open and close at different times during the action potential. When a channel is opened, there is increased electrical conductance (g) of specific ions through that ion channel. Closure of ion channels causes ion conductance to decrease. As ions flow through open channels, they generate electrical currents (i or I) that change the membrane potential.

Atropine inhibits the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves, and on smooth muscles, which respond to endogenous acetylcholine but are not so innervated it is a medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate and to decrease saliva production during surgery. It is typically given intravenously or by injection into a muscle.

2)increase heart rate, the autonomic nervous system increases sympathetic outflow to the SA node, with concurrent inhibition of vagal tone. Norepinephrine released by sympathetic activation of the SA node binds to beta-adrenoceptors.

3) acetylcholine, or a combination thereof on the action potential configuration of rabbit SA nodal and left atrial myocytes. Action potentials were recorded under close-to-physiological conditions. The temperature of the bath solution was maintained at 36°C and the amphotericin-perforated patch-clamp technique was used to minimize intracellular dialysis, thus maintaining the integrity of second-messenger systems. To the best of our knowledge, the present study is the first in which the effects of noradrenalin, acetylcholine, or a combination thereof on the action potential configuration of isolated sinoatrial and atrial myocytes has been tested in detail under such close-to-physiological conditacetylcholine and noradrenalin can modulate the beating rate of SA nodal myocytes and the action potential duration of atrial myocytes over a wide range. If specific SA nodal RGS protein isoforms exist that suppress muscarinic or adrenergic sensitivity of the SA node, they may prove therapeutical targets for the treatment of SA nodal bradycardia or tachycardia. Atrial-specific RGS protein isoforms may prove useful as therapeutical targets to increase the adrenergic sensitivity of atrial cells, thereby increasing their action potential duration and refractory period and thus decreasing the risk of atrial tachycardia and fibrillation. This will, however, require a large body of research before one can think of clinical translation.ions.

As detaile our SA nodal and atrial myocytes showed clearly distinct action potential characteristics. We obtained our myocytes from rabbit, which is a widely used animal model in the field of cardiac cellular electrophysiology. In many respects, human action potential morphology is better resembled by rabbit than by mouse.qYet, one should be aware that there may be species differences in the underlying mechanisms, as there are, e.g., in calcium handling and adenylate cyclase activity between mouse and man.