Question

How do pacemaker cells generate a rhythmic action potential? What makes them autorhythmic?

Answer 1

a)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.-

1.Phase 4-The spontaneous depolarization (pacemaker potential) that triggers the action potential once the membrane potential reaches threshold between -40 and -30 mV).

2.Phase 0-The depolarization phase of the action potential.

3.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 that change the membrane potential.

In the SA node, three ions are particularly important in generating the pacemaker action potential. The role of these ions in the different action potential phases are described below:

*At the end of repolarization, when the membrane potential is very negative (about -60 mV), ion channels open that conduct slow, inward (depolarizing) Na+ currents. These currents are called funny currents. These depolarizing currents cause the membrane potential to begin to spontaneously depolarize, thereby initiating Phase 4. As the membrane potential reaches about -50 mV, another type of channel opens. This channel is called transient or T-type Ca++ channel. As Ca++ enters the cell through these channels down its electrochemical gradient, the inward directed Ca++ currents further depolarize the cell. When the membrane depolarizes to about -40 mV, a second type of Ca++ channel opens. These are the so-called long-lasting, or L-type Ca++ channels. Opening of these channels causes more Ca++ to enter the cell and to further depolarize the cell until an action potential threshold is reached (usually between -40 and -30 mV). During Phase 4 there is also a slow decline in the outward movement of K+ as the K+ channels responsible for Phase 3 continue to close. This fall in K+ conductance (gK+) contributes to the depolarizing pacemaker potential.

*Phase 0 depolarization is primarily caused by increased Ca++ conductance (gCa++) through the L-type Ca++ channels that began to open toward the end of Phase 4. The "funny" currents, and Ca++ currents through the T-type Ca++ channels, decline during this phase as their respective channels close. Because the movement of Ca++ through these channels into the cell is not rapid, the rate of depolarization (slope of Phase 0) is much slower than found in other cardiac cells (e.g., Purkinje cells).

* Phase 3 Repolarization occurs as K+ channels open (increased gK+) thereby increasing the outward directed, hyperpolarizing K+ currents. At the same time, the L-type Ca++ channels become inactivated and close, which decreases gCa++ and the inward depolarizing Ca++ currents.

b) The contraction of cardiac muscle (heart muscle) in all animals is initiated by electrical impulses known as action potentials. The rate at which these impulses fire, controls the rate of cardiac contraction, that is, the heart rate. The cells that create these rhythmic impulses, setting the pace for blood pumping, are called pacemaker cells, and they directly control the heart rate. They make up the cardiac pacemaker, that is, the natural pacemaker of the heart. In most humans, the concentration of pacemaker cells in the sinoatrial (SA) node is the natural pacemaker, and the resultant rhythm is a sinus rhythm.