The time course of sodium inactivation in squid giant axons.

1. The time course of Na inactivation was studied in intact and perfused squid giant axons under voltage-clamp conditions. 2. The pulse programme consisted of a conditioning pulse of varying duration, followed after an interval of 3-8 msec by test pulse. The measurements were done in sea water with 1/3 or 1/5 of the normal Na concentration. In most experiments a 100 microseconds conditioning pulse was sufficient to reduce INa peak elicited by the test pulse. In some experiments even a 50 microseconds conditioning pulse produced a clear reversible decrease of INa peak. We conclude that the upper limit for an initial delay in the development of inactivation is 50-100 microseconds; this applies to temperatures between 0 and 13 degrees C and membrane potentials between -40 and 15 mV. The decrease of INa peak with increasing duration of the conditioning pulse was consistent with an exponential decay starting at 50 or 100 microseconds. 3. With large Na currents in full Na sea water the time course of inactivation became sigmoid. This is attributed to a long-lasting tail of inward current which follows the conditioning pulse and produces a voltage drop across the series resistance. 4. If the conditioning pulse and the test pulse were not separated by an interval, INa peak showed a sigmoid dependence on the duration of the conditioning pulse. This phenomenon is predicted by the equations of Hodgkin & Huxley (1952) as first pointed out by Kniffki, Siemen & Vogel (1978). With sufficiently strong conditioning pulses INa peak could even increase in size.