Sodium channel kinetics in normal and denervated rabbit muscle membrane

The effects of chronic denervation on sodium (Na) channels in rabbit muscle membrane were determined using intracellular microelectrodes and Vaseline gap voltage clamp techniques. The Hodgkin-Huxley model was used to describe the kinetic and steady-state parameters of channel activation and fast inactivation. Chronic (7-10 days) denervation was found to cause a decreased resting potential, lowered action potential peak, and fibrillation potentials in rabbit extensor digitorum longus (EDL) muscles. Under voltage clamp conditions, no differences were observed between denervated and normal fibers in the voltage dependence of the steady-state Na channel activation and fast inactivation curves, or in the time course of development of fast inactivation. However, in denervated fibers, the time course of recovery from fast inactivation was approximately half that measured in normal fibers. Also, whereas depolarizing holding potentials induced a long-term inactivation to varying degrees in normal EDL fibers, denervated EDL fibers and normal soleus fibers were uniformly resistant to prolonged depolarization. These results suggest that the denervation-induced development of spontaneous activity may be due in part to changes in the mechanisms that control the refractoriness of Na channels.