TIME-DEPENDENT CHANGES IN KINETICS OF NA+ CURRENT IN SINGLE CANINE CARDIAC PURKINJE-CELLS

The spontaneous hyperpolarizing shift in Na+ channel kinetics that occurs during a series of voltage-clamp recordings was characterized in single canine cardiac Purkinje cells at 10-13.5-degrees-C. The change in the half-point of voltage-dependent availability, in the half-point of peak conductance, in the voltage dependence of deactivation and time to peak Na+ channel current (I(Na)), and in the time constants of I(Na) decay in response to step depolarizations were examined. The half points of availability and conductance shifted similarily, -0.41 +/- 0.13 and -0.47 +/- 0.19 mV/min, respectively (n = 14). These were directly correlated (slope 1.14 +/- 0.06, R2 = 0.81) with conductance shifting on average only -0.05 mV/min faster than availability. The deactivation time constant-voltage relationship shifted similarily to availability and conductance. Tail current decay time constants predicted the voltage dependence of the open to closed transition to be 0.9e-. Time to peak I(Na) in response to step depolarizations changed e-fold for 25 mV but plateaued at positive potentials (531-mu-s, n = 22). I(Na) decay was multiexponential between -40 and 80 mV. Decay time constants changed little as a function of voltage at positive potentials. The contribution of the second time constant to decay amplitude was 15-20% over the entire voltage range. Time to peak I(Na) shifted in a curvilinear fashion, changing less late in an experiment. We conclude that the channel-voltage sensor responds to a changing fraction of the applied voltage during an experiment, producing similar rates of shift of voltage-dependent availability, conductance, and deactivation time constants.