Sodium channel opening as a precursor to inactivation. A route to the inactivated state.

The time constant of the process producing the delay in Na inactivation development as determined by the two pulse method (tau delay) was extracted and compared to that of the slowest Na activation process (tau 3) for the INa during the conditioning pulse of that same determination. tau delay and two pulse inactivation (tau C) values were computer generated using a non-linear least squares algorithm. tau 3 and single pulse inactivation (tau h) values were independently generated for each determination also with the aid of the computer using the same non-linear least squares algorithm. In one determination at 2 mV, tau C was 4.68 and tau delay 0.494 ms while tau h was 4.70 and tau 3 0.491 ms for a tau c/tau h of 0.996 and a tau delay/tau 3 of 1.006. Mean tau delay/tau 3 from five determinations in four axons, both Cs and K perfused, and spanning a potential range of -27 to 2 mV was 1.068. The precursor process to inactivation is channel opening. Some fraction of channels presumably inactivate via another route where prior channel opening is not required.