In vivo assessment of muscle membrane properties in the sodium channel myotonias

Abstract

INTRODUCTION: The gain-of-function mutations that underlie sodium channel myotonia(SCM) and paramyotonia congenita(PMC) produce differing clinical phenotypes. We used muscle velocity recovery cycles (MVRCs) to investigate membrane properties. METHODS: MVRCs and responses to trains of stimuli were compared in patients with SCM (n=9), PMC (N=8), and normal controls (n=26). RESULTS: The muscle relative refractory period was reduced in SCM, consistent with faster recovery of the mutant sodium channels from inactivation. Both SCM and PMC showed an increased early supernormality, and increased mean supernormality following multiple conditioning stimuli, consistent with slowed sodium channel inactivation. Trains of fast impulses caused a loss of amplitude in PMC, after which only half of the muscle fibres recovered, suggesting that the remainder stayed depolarized by persistent sodium currents. DISCUSSION: The differing effects of mutations on sodium channel function can be demonstrated in human subjects in vivo using this technique