Na activation delays and their relation to inactivation in frog skeletal muscle

Delays in the development of activation of Na currents were studied using voltage-clamped frog skeletal muscle fibers. Na currents elicited by a depolarizing voltage step from a hyperpolarized membrane potential were delayed in their activation when compared to Na currents elicited from the resting potential. The magnitude of the delay increased with larger hyperpolarizing potentials and decreased with larger depolarizing test potentials. Delays in activation observed following chloramine-T treatment that partially removes inactivation did not differ from delays observed before treatment. Longer exposures of the muscle fiber to chloramine-T led to a complete loss of inactivation, coincident with an elimination of the hyperpolarization-induced delays in activation. Steady-state slow inactivation was virtually unaffected by prolonged exposures of the fibers to chloramine-T that eliminated fast inactivation. The results show that chloramine-T acts at a number of sites to alter both activation and inactivation. Markov model simulations of the results show that chloramine-T alters fundamental time constants of the system by altering both activation and inactivation rate constants.