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The anesthetic propofol modulates gating in paramyotonia congenita mutant muscle sodium channels
Author(s) -
Haeseler Gertrud,
Störmer Martina,
Mohammadi Bahram,
Bufler Johannes,
Dengler Reinhard,
Piepenbrock Siegfried,
Leuwer Martin
Publication year - 2001
Publication title -
muscle and nerve
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.025
H-Index - 145
eISSN - 1097-4598
pISSN - 0148-639X
DOI - 10.1002/mus.1064
Subject(s) - sodium channel , propofol , chemistry , skeletal muscle , anesthetic , patch clamp , gating , depolarization , biophysics , anesthesia , pharmacology , sodium , sodium channel blocker , electrophysiology , endocrinology , medicine , biology , organic chemistry
We examined the effects of propofol on a paramyotonia congenita mutant skeletal 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 channel myopathies. Our hypothesis was that propofol might interact directly with mutant channels, causing enhanced muscle excitability in affected patients. Whole‐cell voltage‐clamp experiments were performed on HEK 293 cells expressing R1448H mutant sodium channels. Propofol blocked sodium inward current at clinical concentrations (5 μmol/L) when depolarizing pulses were started from holding potentials close to the physiological resting potential (−70 mV). Higher propofol concentrations (≥25 μmol/L) accelerated pathologically delayed inactivation kinetics and delayed 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 experienced by affected patients in vivo. © 2001 John Wiley & Sons, Inc. Muscle Nerve 24: 736–743, 2001