MUSCLE SODIUM-CHANNEL INACTIVATION DEFECT IN PARAMYOTONIA-CONGENITA WITH THE THR1313MET MUTATION

Mutations of the skeletal muscle sodium (Na) channel have been reporte d in families with paramyotonia congenita (PC), an autosomal dominant disorder with cold and/or exercise induced stiffness and myotonia. Fun ctional consequences of specific Na channel mutations responsible for PC have not been described. Patch clamp recording of single Na channel s were made in cultured myotubes at 22 and 34 degrees C from a PC pati ent with the thr1313met mutation. Cell-attached and outside-out record ings of mutant PC channels contained long duration and late openings. The mean open time was increased and the ensemble average showed a pro longed inward Na current. This membrane depolarization could cause rep etitive action potentials and the clinical syndrome.