The effect of external potassium on the removal of sodium inactivation in squid giant axons.

1. The effect of external and internal electrolytes on the parameters of the Na conductance, in particular on the time constant of removal of Na inactivation, was studied in intact and perfused squid giant axons under voltage-clamp conditions. 2. Adding 20-40 mM-KCl, -CsCl or -RbCl to K-free sea water reversibly increased the time constant of removal of inactivation by a factor of about 1.3; adding 20 mM-NaCl had no effect. The time constant of development of inactivation was decreased. The results are consistent with a -5 mV shift of the tau h(V) curve. The sodium activation (m infinity 3) and inactivation (h infinity) curves were shifted by the same amount. 3. Raising external Ca, by contrast, decreased the time constant of removal of inactivation and increased the time constant of development of inactivation, i.e. shifted the tau h(V) curve to more positive internal potentials. A free Ca concentration of 0.1 mM in the internal solution had no effect on Na inactivation. 3. The observations are compatible with the idea that external K, Cs or Rb interfere with the binding of Ca to negative fixed charges at the outer side of the membrane, thereby causing a shift in the opposite direction to the shift produced by raising external Ca. 5. Replacing two thirds of the internal K by Na reversibly increased the time constant of removal of sodium inactivation and moved the tau h(V) curve in the vertical direction.