Sodium current in single heart muscle cells

Abstract

A COMPLETE description of the sodium current, I_Na, in heart muscle has not been obtained despite the practical importance of such information as a rational basis for the therapy of arrhythmias. I_Na has been examined under voltage clamp using micropipette¹ or sucrose gap methods², but the adequacy of spatial control of voltage has been questioned and temporal resolution of the early kinetics has been unsatifactory and results therefore inconclusive³. These problems reflect the fact that heart muscle is a syncytium with restricted extracellular compartments. One of the more favourable preparations is rabbit Purkinje fibres⁴ and Colatsky and Tsien⁵ have recently performed voltage clamp studies on them with the two micro-pipettes technique. They have demonstrated the feasibility of this approach when proper precautions are taken⁵. Quite a different approach has been taken by other investigators such as Mehdi and Sachs⁶ and Powell et al.^7–9, who have dispersed individual heart muscle cells and examined them with micropipette techniques. In this way the complex geometry is greatly simplified although the enzymes used in dispersion may pose another set of problems. We have followed this second approach and have isolated individual heart muscle cells from adult rats with a modified version of the dispersion method reported by Powell and Twist⁹. To perform electrophysiological studies we have sucked single cells into a suction pipette and used a technique which allows voltage clamp and internal perfusion¹⁰. I_Na has been isolated by suppression of other cardiac currents and its kinetics separated from the capacitative current transient. The success of the present approach indicates its potential usefulness in cardiac electrophysiology.