Voltage dependent modification of sodium channel gating with water-soluble carbodiimide.

Currents through sodium channels in frog myelinated fibre were measured before and after the treatment of the membrane with water-soluble carbodiimide (WSC). The WSC treatment produces dramatic changes both in activation and inactivation when membrane potential during the treatment is held at levels from -80 to -100 mV. Both gating processes are slowed and their voltage dependence is reduced. The effective charge of activation as measured by limiting logarithmic potential sensitivity is reduced after 10 min of the WSC treatment by the factor of 1.66. The same WSC treatment applied at zero potential induced no change in the effective charge of activation. Other parameters of gating are changed after such treatment but to a lesser degree and in a somewhat different fashion than after the treatment at high negative potential. The results are consistent with the hypothesis that part of a mobile gating charge is presented by carboxyl groups migrating from the external surface to the interior of the channel molecule when the channel opens or inactivates.