Differential effects of halothane on adult and juvenile sodium channels in human muscle

Abstract

Myoballs were cultured from biopsies of adult human skeletal muscle. Transient currents through the sodium channels were elicited by depolarizing a myoball membrane with the whole-cell patch-clamp technique. The properties of the sodium channels were determined from the Hodgkin-Huxley parameters (I _{Na max}, τ_m, τ_h,h _∞-curve) derived from these transients. Halothane, when applied at 3.4 mmol/l (≈15 kPa), blocked about 50% of the current through the adult, TTX-sensitive sodium channels but had little effect on the current through the juvenile, TTX-insensitive sodium channels. At >12 mmol/l, halothane blocked both channel types completely. The time constants of activation and inactivation were decreased in the presence of 3.4 mmol/l halothane but not enough to account for the decrease of the current amplitude. Halothane shifted the h_∞-curves of both channel types towards more negative potentials by an amount that was roughly proportional to its concentration. Myoballs from a man susceptible to malignant hyperthermia (MH) gave the same results as the controls indicating that the halothane effects on the action potential of MH-susceptible muscle are not mediated by a specific effect on the sodium channels.