The Pacemaker Potential

Although the ionic mechanism of the cardiac action potential differs in important ways from that of other action potentials, nothing in the scheme presented so far would account for the endogenous beating of isolated heart cells discussed earlier. If we recorded the electrical membrane potential of a spontaneously beating isolated heart cell, we would see a series of spontaneous action potentials, as shown in Figure 12-7. After each action potential, the potential falls to its normal negative resting value, then begins to depolarize slowly. This slow depolarization is called a pacemaker potential, and it is caused by spontaneous changes in the membrane ionic permeability. Voltage-clamp experiments on single isolated muscle fibers from the ventricles suggest that the pacemaker potential is due to a slow decline in the potassium permeability coupled with a slow increase in sodium and calcium permeability. When the depolarization reaches threshold, it triggers an action potential in the fiber, with a rapid upstroke caused by opening of sodium channels and a prolonged plateau produced by calcium channels. Part of the early phase of the pacemaker potential represents the normal undershoot period of an action potential (see Chapter 6), when potassium channels that were opened by depolarization during the action potential slowly close again. As these potassium channels close, the membrane potential will move in a positive direction, away from the potassium equilibrium potential.

Action potential

Time

Pacemaker potential

"v

Time

Pacemaker potential

"v

Action potential

0.5 sec

Figure 12-7 A recording of the membrane potential during repetitive, spontaneous beating in a single cardiac muscle fiber. The repolarization at the end of one action potential is followed by a slow, spontaneous depolarization called the pacemaker potential. When this depolarization reaches threshold, a new action potential is triggered.

Figure 12-8 Diagram of the spread of action potentials across the heart during a single heartbeat. The excitation originates in the sinoatrial (SA) node of the right atrium and spreads throughout the atria via electrical coupling among the atrial muscle fibers. The fibers of the atria are not electrically connected to those of the ventricles. The action potential spreads to the ventricles via the atrioventricular (AV) node, which introduces a delay between the atrial and ventricular action potentials. When the wave of action potentials leaves the AV node, its spread throughout the ventricles is aided by the rapidly conducting Purkinje fibers of the bundle of His.

Later phases of the pacemaker potential represent increases in sodium and calcium permeability, both of which move the membrane potential more positive, toward the sodium and calcium equilibrium potentials. The sodium permeability increases during the pacemaker potential because of the opening of nonspecific cation channels, which open at more hyperpolarized membrane potentials. As described in Chapter 8, the opening of channels with equal permeability to sodium and potassium ions (like the ACh-activated channels at the neuromuscular junction) will produce depolarization of a cell. These hyperpolarization-activated cation channels are opened in response to the membrane hyperpolarization during the undershoot of the action potential. Together with the decrease in potassium permeability, the resulting influx of sodium ions moves the membrane potential of the cardiac cell in a positive direction, toward the threshold for firing an action potential. As the membrane potential becomes more positive during the pacemaker potential, voltage-dependent calcium channels open in response to the depolarization. The resulting influx of positively charged calcium ions produces even more depolarization, ultimately triggering the next action potential in the series.

The rate of spontaneous action potentials in isolated heart cells varies from one cell to another; some cells beat rapidly and others slowly. In the intact heart, however, the electrical coupling among the fibers guarantees that all the fibers will contract together, with the overall rate being governed by the fibers with the fastest pacemaker activity. In the normal functioning of the heart, the overall rate of beating is controlled by a special set of pacemaker cells, called

the sinoatrial (SA) node, which is located in the upper part of the right atrium. This node is indicated in the diagram of the heart in Figure 12-8. The action potential of cells in the SA node is a bit different from that of other cardiac cells. In the SA node, calcium channels play a larger role than sodium channels in triggering the action potential, as well as in sustaining the depolarization during the action potential. In the normal resting human heart, the cells of the SA node generate spontaneous action potentials at a rate of about 70 per minute. These action potentials spread through the electrical connections among fibers throughout the two atria, generating the simultaneous contraction of the atria as discussed in the first section of this chapter. This helps insure that the two atria contract together. The atrial action potentials do not spread directly to the fibers making up the two ventricles, however. This is a good thing, because we know that the contraction of the ventricles must be delayed to allow the relaxed ventricles to fill with blood pumped into them by the atrial contraction. In terms of electrical conduction, the heart behaves as two isolated units, as shown in Figure 12-8: the two atria are one unit and the two ventricles are another. The electrical connection between these two units is made via another specialized group of muscle fibers called the atrioventricular (AV) node. Excitation in the atria must travel through the AV node to reach the ventricles. The fibers of the AV node are small in diameter compared with other cardiac fibers. As discussed in Chapter 6, the speed of action potential conduction is slow in small-diameter fibers. Therefore, conduction through the AV node introduces a time delay sufficient to retard the contraction of the ventricles relative to the contraction of the atria. Excitation leaving the AV node does not travel directly through the muscle fibers of the ventricles. Instead, it travels along specialized muscle fibers that are designed for rapid conduction of action potentials. These fibers are called Purkinje fibers, and they form a fast-conducting pathway through the ventricles called the bundle of His. The Purkinje fibers carry the excitation rapidly to the apex at the base of the heart, where it then spreads out through the mass of ventricular muscle fibers to produce the contraction of the ventricles.

0 0

Post a comment