Utrophin suppresses low frequency oscillations and coupled gating of mechanosensitive ion channels in dystrophic skeletal muscle

摘要: An absence of utrophin in muscle from mdx mice prolongs the open time single mechanosensitive channels. On a scale much longer than duration individual channel activations, genetic depletion produces low frequency oscillations probability. Oscillatory opening occurred dystrophin/utrophin mutants, but was absent wild-type and fibers. By contrast, small conductance channels showed random gating behavior when present same patch. Applying negative pressure to patch on DKO fiber produced burst mode II activity, subsequently closed remained silent for tens seconds during maintained stimulus. In addition, simultaneous multiple MS could be frequently observed recordings patches fibers, only rarely muscle. A model which accounts single-channel data is proposed acts as spring maintains mechanical stability caveolar-like compartment. The state this compartment suggested dynamic; its continuity with extracellular surface varying over minutes. Loss contributes pathogenic Ca(2+) entry through Duchenne dystrophy.