The impact of single cell voltage clamp on the understanding of the cardiac ventricular action potential.

In this article we review results obtained during the last decade by the single cell voltage clamp technique on cardiac ventricular myocytes, and we re-evaluate the major ionic currents underlying the cardiac action potential. Since its introduction into cardiac electrophysiology in the late seventies this technique has greatly contributed to our knowledge about the role of the transmembrane ionic currents in the heart. Recent findings gained with this method have confirmed that the inward sodium current is responsible not only for the fast depolarization, but, in part, also for the maintenance of the plateau phase of the action potential. The kinetics of the inward calcium current measured by the single cell voltage clamp technique proved to be much faster than was previously thought. In addition, two types of the inward calcium current with different physiological roles have recently been identified. The L-type calcium current plays an important part in maintaining the plateau phase of the action potential and may cause depolarization at less negative potentials. Although the physiological significance of the T-type calcium current is less clear, it appears to be involved in the pacemaker function of cardiac tissues. Single cell voltage clamp experiments have shown that the inward rectifier potassium current is not independent of time, as described earlier, but it helps to terminate the final phase of repolarization, and presumably controls the resting membrane potential. Recent studies with the single cell voltage clamp method have revealed that the delayed rectifier potassium current has, most probably, more than one component and is extensively modulated by neurotransmitters. Its main role is to initiate and terminate cardiac repolarization. This current is of particular importance in regulating rate-dependent repolarizations. The transient outward current, which rapidly activates and inactivates after depolarization, initiates early fast repolarization and may also take part in rate-dependent repolarization. The ionic carriers of this current are most likely potassium and chloride. The use of the single cell voltage clamp technique has led to the discovery of formerly unrecognized currents, like the ATP-dependent potassium current, the sodium activated potassium current and the chloride currents. The application of the new technique has made it possible to focus more attention on currents which were difficult to study previously, such as Na/K pump and Na/Ca exchanger currents.