Reduction of myosin-light-chain phosphorylation and of parvalbumin content in myotonic mouse muscle and its reversal by tocainide

Abstract

In muscle of the myotonic mouse mutant, 'arrested development of righting response', ADR, a reduced level of fast-myosin-light-chain-2 (LC2f) phosphorylation was observed in addition to a lowered parvalbumin content. In fast muscles, average phosphorylation levels of LC2f (LC2-P/LC2 total) were 0.76 mol/mol for wild type and 0.59 mol/mol for the myotonic mutant. The difference was not due to short-term activity prior to freezing because it was also found in curare-paralyzed muscles. Long-term treatment of genetically myotonic animals with the membrane-stabilizing drug, tocainide, led to an increase of parvalbumin content and LC2-P level. In wild-type mice, tocainide had a similar effect, leading to supranormal parvalbumin concentrations. It is concluded that both the basal level of LC2-P and parvalbumin concentration are regulated by a common factor, related to long-term muscle activity.