STUDY OF THE INACTIVATING COMPONENT OF THE ASYMMETRICAL DISPLACEMENT CURRENT IN FROG NERVE-FIBER

The inactivating component of the asymmetrical displacement current in frog (Rana ridibunda) nerve was studied by means of a linearly changing (ramp) voltage. Steady state inactivation of the inactivating component, measured as the relative amount of mobile charge, follows the same dependence on membrane potential as steady state inactivation of Na permeability (h.infin.) does. Upon immobilization of some fraction of the charge by the inactivation mechanism, the distribution of those charges remaining free to move becomes less steep, the midpoint of distribution being shifted in a hyperpolarizing direction. (Charge distribution is the fraction of the total mobile charge that has moved from the resting state, as a function of the membrane potential.) Under the ramp voltage, Na activation attains values which correspond to the quantity of charge in the activating position in steady state conditions, with a delay which is more pronounced at low values of charge transferred. A formal description of the activation of Na permeability in terms of the inactivating component of the displacement current is considered in which rate constants of the process which executes the gating of the Na channel are functions of the relative number of charges transferred from the resting to the activating position. The physical background of this formal description is based on the concept that each Na channel is controlled by an ensemble of polar activating subunits with small dipole moments which are incorporated in a co-operative system by some, presumably short order, interactions. The co-operativity concept makes it possible to account for the nonlinear behavior of a charged system with respect to inactivation.