The cardiac action potential

Intracellular recordings from heart muscle fibres were first made using isolated bundles of Purkinje fibres from dogs. The Purkinje fibres form a spe-

Intercalated discs

Intercalated discs

Fig. 11.1. Mammalian heart muscle cells.
Hearet Action Potential

500 ms

Fig. 11.2. The cardiac action potential. Based on the action potentials produced spontaneously in isolated Purkinje fibres.

500 ms

Fig. 11.2. The cardiac action potential. Based on the action potentials produced spontaneously in isolated Purkinje fibres.

cialized conducting system which serves to carry excitation through the ventricle. After being isolated for a short time, they begin to produce rhythmic spontaneous action potentials, of the sort shown diagrammatically in Fig. 11.2. The form of these action potentials differs from those of nerve axons and twitch skeletal muscle fibres in that there is a prolonged 'plateau' between the peak of the action potential and the repolarization phase. The action potential is preceded by a slowly-rising pacemaker potential, which acts as a trigger for the action potential when it crosses a threshold level.

What is the ionic basis of these heart muscle action potentials? The peak membrane potential is reduced when the external sodium ion concentration is lowered. This suggests that the initial rapid depolarization is brought about by a regenerative increase in the sodium conductance of the membrane, just as in the action potential of nerve axons. However, cardiac action potentials must involve phenomena which are absent from nerve axons, in order to explain the plateau and the pacemaker potential.

Sorting out the full nature of the cardiac action potential has proved to be a complicated task. In comparison with squid axons, the size and geometry of heart muscle fibres makes it much harder to subject them to voltage-clamp, and the number of different ion channels involved in the action potential is larger. A computer model, based on voltage-clamp measurements on Purkinje fibres, has been produced by D. DiFrancesco and D. Noble; let us have a brief look at it.

There are four ionic conductances involved in the model. The sodium conductance gNa is rapidly activated and then inactivated by depolarization, and blocked by tetrodotoxin; it is essentially similar to the sodium conductance of nerve and skeletal muscle cells. The potassium conductance gK is complex (at least three different types of channel seem to be involved), with some components being activated by hyperpolarization and others by depolarization. There is an appreciable calcium conductance gCa which is activated by depolarization and produces inward current during the plateau. A fourth conductance gf permits the slow inward movement of sodium and other ions; it is activated by hyperpolarization and is important during the pacemaker potential.

The sequence of events in the DiFrancesco—Noble model is shown in Fig. 11.3. Let us begin at the point in the cycle where the membrane potential is at its most negative, at about 0.4 ms on the time trace. It has reached this negative value because the potassium conductance gK is high. However, the pacemaker conductance gf has been switched on by the hyperpolarization, and it rises steadily for the next second or so. The slow sodium ion inflow which this permits results in a steady depolarization, the pacemaker potential. After a time the pacemaker potential has depolarized the membrane sufficiently to open the fast-activating sodium channels. Then follows the familiar runaway relation between membrane potential and sodium conductance just as in the nerve axon, so that there is a massive inflow of sodium ions and a rapid overshooting depolarization. This increase in sodium conductance is rapidly inactivated (the sodium channels close again) so that the membrane potential rapidly falls back from its positive peak, just as in the nerve action potential.

But now the model departs radically from the situation in nerve axons. The potassium conductance has fallen to a low level and there is an elevated calcium conductance, hence the membrane potential remains near zero for some hundreds of milliseconds. This plateau declines gradually and is brought to an end as a result of the long-delayed increase in potassium conductance, and any calcium and fast sodium channels remaining open are finally closed

Conductance

Fig. 11.3. Computer simulation of the cardiac action potential. The associated conductance changes are shown in the lower graphs: gf is the inward current which becomes apparent during the pacemaker potential. The sodium conductance gNa includes both the conductance due to fast sodium channels and the sodium component of gf. From DiFrancesco and Noble (1985).

Fig. 11.3. Computer simulation of the cardiac action potential. The associated conductance changes are shown in the lower graphs: gf is the inward current which becomes apparent during the pacemaker potential. The sodium conductance gNa includes both the conductance due to fast sodium channels and the sodium component of gf. From DiFrancesco and Noble (1985).

during the repolarization phase. By the end of the action potential the pacemaker conductance gf has already begun to rise and so the new cycle continues on its way.

The heart muscle cell membrane is refractory for a long time — some hundreds of milliseconds — after the completion of an action potential. Consequently it is not possible to tetanize heart muscle by repetitive stimulation, since the refractory period is long enough to allow the muscle to relax after each action potential. This is of vital importance to the functioning of the heart as a pump: the relaxation phase allows the heart to be refilled with blood from the veins before expelling it to the arteries during the contraction phase.

The long duration of the cardiac action potential as compared with that in a twitch skeletal muscle fibre is related to an important difference in their

Action potential

Action potential

Cardiac muscle

Fig. 11.4. Diagram comparing the relative time scales of the electrical and mechanical responses in skeletal and cardiac muscle. From Noble (1979).

roles in excitation—contraction coupling. In the skeletal muscle the action potential acts simply as a trigger which initiates the resulting contraction but has no further control over it. But in the cardiac muscle the action potential is coincident with most of the contraction phase, and indeed relaxation begins during the repolarization phase (Fig. 11.4). If the action potential is shortened in some way, relaxation begins sooner and so the tension reaches a lower peak level; the reverse happens if the action potential is lengthened. Hence the action potential acts as a controller of the contraction as well as a trigger for it.

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