Inactivation of cardiac Na+ channel simply through open states as revealed by single-channel analysis in guinea pig ventricular myocytes.
Inactivation of the cardiac Na(+) channel was analyzed by recording channel currents from a cell-attached patch containing only one functional Na(+) channel in guinea-pig ventricular myocytes. A two-step test pulse, first to variable levels (Pulse 1) and then to -30 mV (Pulse 2) was applied from a holding potential of -140 mV. When a cumulative histogram was determined for the latency of first opening, the histogram was well fitted with a single exponential function at -70 to -30 mV of Pulse 1. The activation time course of ensemble average was virtually single exponential. Although the ensemble average of 500 sweeps showed various extents of inactivation during Pulse 1, the saturation level of the cumulative first-latency histogram at the end of the two-step pulse was almost constant (0.7-0.8), irrespective of Pulse 1. Even when the interval between successive test pulses was prolonged from 70 to 970 ms, the saturation level of the histogram was not modified. These findings are consistent with inactivation only through the open state. Thus, the apparent "blank sweep inactivation" does not necessarily indicate direct inactivation from closed states. These findings support the hypothesis that the inactivation of cardiac Na(+) channel occurs exclusively through the open state.
Mitsuiye
Tamotsu
T
Department of Physiology, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto, 606-8501 Japan. tamo3@card.med.kyoto-u.ac.jp
Noma
Akinori
A
D000818:Animals; D004558:Electric Stimulation; D004594:Electrophysiology; D006168:Guinea Pigs; D006352:Heart Ventricles; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D011930:Reaction Time; D015222:Sodium Channels / Q000378:metabolism* / Q000502:physiology
D015222:Sodium Channels