Exponential activation of the cardiac Na+ current in single guinea-pig ventricular cells

Abstract

1. The cardiac Na+ current of guinea-pig was recorded using an improved oil-gap voltage clamp method. When a single ventricular cell was stretched between the internal and external solution compartments across an oil gap of about 40 microns in width, the sealing resistance in the oil gap was higher than 1 G omega and the time constant of the capacitive current was between 10 and 40 microseconds. Effective series resistance (Rs) was less than 50 k omega after Rs compensation. 2. The activation time course (I'Na) was separated from inactivation by dividing the digitized record of Na+ current with the inactivation variable h(t), which was obtained by fitting exponential functions to the decaying phase of current. I'Na started as a single exponential activation at time 0, which was defined by the decay of the capacitive current to 5% of its peak. 3. The Na+ tail current was recorded on repolarization after a short (1.2 ms) depolarizing pulse to -10 mV. Its single exponential decay at potentials negative to -50 mV, or its major exponential component of decay between -50 and -30 mV, was attributed to deactivation. The time constants of deactivation were similar to those of activation which were measured from I'Na on depolarization to comparable potentials. The m1 kinetics gave a better fit for Na+ activation than the m3 kinetics. 4. The time constant of deactivation was a linear function of the membrane potential on a semilogarithmic scale with an e-fold increase per 21.6 +/- 1.3 mV (n = 8) depolarization. The steady-state activation value (m(infinity)) was obtained from the amplitude of I'Na. Fitting a Boltzmann equation indicated a half-activation potential of -21.9 +/- 1.7 mV and a slope factor of 7.9 +/- 0.4 mV (n = 9). 5. m1 kinetics are more pertinent to a description of the cardiac Na+ current. Limitations in analysing the activation kinetics of Na+ current are discussed for the improved oil-gap voltage clamp method.