The anesthetic propofol modulates gating in paramyotonia congenita mutant muscle sodium channels

We examined the effects of propofol on a paramyotonia congenita mutant skel etal muscle sodium channel in vitro, because life threatening complications resulting from severe muscle rigidity during induction of anesthesia have been observed using other anesthetics in patients with hereditary sodium ch annel myopathies. Our hypothesis was that propofol might interact directly with mutant channels, causing enhanced muscle excitability in affected pati ents. Whole-cell voltage-clamp experiments were performed on HEK 293 cells expressing R1448H mutant sodium channels. Propofol blocked sodium inward cu rrent at clinical concentrations (5 mu mol/L) when depolarizing pulses were started from holding potentials close to the physiological resting potenti al (-70 mV). Higher propofol concentrations (greater than or equal to 25 mu mol/L) accelerated pathologically delayed inactivation kinetics and delaye d pathologically enhanced recovery from inactivation. Our in vitro results show that inactivation-deficient sodium channels are specifically targeted and blocked by propofol. This might reduce enhanced muscle excitability exp erienced by affected patients in vivo. (C) 2001 John Wiley & Sons, Inc.