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Paramyotonia congenita: The R1448P Na + channel mutation in adult human skeletal muscle
Author(s) -
Lerche H.,
Mitrovic N.,
Dubowitz V.,
LehmannHorn F.
Publication year - 1996
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410390509
Subject(s) - sodium channel , skeletal muscle , chemistry , depolarization , myotonia congenita , repolarization , membrane potential , biophysics , medicine , endocrinology , sodium , anatomy , electrophysiology , myotonia , biology , biochemistry , organic chemistry , myotonic dystrophy
Twitch force and Na+ currents were investigated in a muscle biopsy specimen from a patient with paramyotonia congenita carrying the dominant Arg‐1448‐Pro mutation in the skeletal muscle sodium channel. Cooling of the muscle fibers caused sustained membrane depolarization that resulted in reduced twitch force. Membrane repolarization, produced by a K+ channel opener, partly prevented and antagonized the drop in twitch force. Patch‐clamp recordings on sarcolemmal blebs revealed a distinctly slower Na + current decay on paramyotonia congenita muscle compared to control muscle. In addition, patches with mutant Na + channels showed a significantly higher frequency of steady‐state openings, which increased with cooling. Activation of mutant channels was not affected, whereas the steady‐state inactivation curve was shifted by −5 mV and showed less voltage dependence. We suggest that the weakness of cooled muscle can be explained by a combination of the increased steady‐state Na + current and the left‐shifted inactivation curve.