Muscle fibers with the Arg-1448-Pro mutation showed slower Na+ current decay, increased steady-state openings with cooling, and a -5 mV shift in the steady-state inactivation curve compared to control.
Case Report (n=1)
The weakness of cooled muscle in paramyotonia congenita with the R1448P mutation is likely due to a combination of increased steady-state Na+ current and a left-shifted inactivation curve.
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.
Lerche et al. (Wed,) conducted a case report in Paramyotonia congenita (n=1). Arg-1448-Pro mutation vs. Control muscle was evaluated on Twitch force and Na+ currents. Muscle fibers with the Arg-1448-Pro mutation showed slower Na+ current decay, increased steady-state openings with cooling, and a -5 mV shift in the steady-state inactivation curve compared to control.
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