MODULATION OF SKELETAL-MUSCLE SODIUM-CHANNELS BY HUMAN MYOTONIN PROTEIN-KINASE

In myotonic muscular dystrophy, abnormal muscle Na currents underlie m yotonic discharges. Since the myotonic muscular dystrophy gene encodes a product, human myotonin protein kinase, with structural similarity to protein kinases, we tested the idea that human myotonin protein kin ase modulates skeletal muscle Na channels, Coexpression of human myoto nin protein kinase with rat skeletal muscle Na channels in Xenopus ooc ytes reduced the amplitude of Na currents and accelerated current deca y, The effect required the presence of a potential phosphorylation sit e in the inactivation mechanism of the channel, The mutation responsib le for human disease, trinucleotide repeats in the 3' untranslated reg ion, did not prevent the effect, The consequence of an abnormal amount of the kinase would be altered muscle cell excitability, consistent w ith the clinical finding of myotonia in myotonic dystrophy.