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

In myotonic muscular dystrophy, abnormal muscle Na currents underlie myotonic 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 kinase modulates skeletal muscle Na channels, Coexpression of human myotonin protein kinase with rat skeletal muscle Na channels in Xenopus oocytes reduced the amplitude of Na currents and accelerated current decay, The effect required the presence of a potential phosphorylation site in the inactivation mechanism of the channel, The mutation responsible for human disease, trinucleotide repeats in the 3' untranslated region, did not prevent the effect, The consequence of an abnormal amount of the kinase would be altered muscle cell excitability, consistent with the clinical finding of myotonia in myotonic dystrophy.