The understanding of ionic currents involved in the excitability of cardiac muscle has improved medical therapy of arrhythmias. Although the cardiac sodium current is an important determinate of excitability, it still has not been well studied because of past limitations in the experimental preparation. Recently a single canine Purkinje cell preparation has been developed that allows for voltage clamp and intracellular perfusion through a single suction electrode. This grant application proposes to apply this new experimental method to investigation of the sodium current and to accomplish the following specific aims: 1. To improve the voltage clamp technique and prove control of the membrane potential during peak INa with an independent microelectrode. 2. To construct instantaneous sodium current IV plots and measure the changes in sodium current to variations in [Na+]o and [Na+]i and compare measured currents to those calculated from the Goldman-Hodgkin-Katz equation. 3. To measure the time course of activation of the sodium current before and after removal of inactivation by N-bromoacetamide. 4. To study inactivation and recovery of inactivation of the sodium current before and after the removal of inactivation by N-bromoacetamide. These studies should advance the understanding of the sodium current and form a solid foundation for the future study of antiarrhythmic drug actions.
| Hanck, D A; Sheets, M F; Fozzard, H A (1990) Gating currents associated with Na channels in canine cardiac Purkinje cells. J Gen Physiol 95:439-57 |
| Sheets, M F; Hanck, D A; Fozzard, H A (1988) Nonlinear relation between Vmax and INa in canine cardiac Purkinje cells. Circ Res 63:386-98 |
