Partial opening and subconductance gating of mechanosensitive ion channels in dystrophic skeletal muscle

摘要: Key points •  Mechanosensitive (MS) channels in skeletal muscle are heteromeric proteins composed of TRPV4 and other subunits. Experiments investigated subconductance fluctuations associated with gating independent subunits. •  MS open by passing through states fluctuate between at least four levels. •  MS mdx spend ∼60% the time smaller levels; applying pressure to membrane increases occupancy fully state. Channels wild-type more state. •  Recordings show partial opening MS that fail reach Partial openings occur ∼3–4 times frequently than muscle. •  During single activations, burst durations charge/burst greater muscle. •  Partial prolonged duration distinct mechanisms contributing excess Ca2+ entry dystrophic muscle Abstract  We recorded activity mechanosensitive ion from mouse, a deletion mutant lacks cytoskeletal protein, dystrophin. were designed examine influence dystrophin, major component costameres, on behaviour channels. In majority recordings cell-attached patches, have conductance ∼23 pS. Recordings some however, showed channel ∼7–14 Large small detected patch serial, non-random gating, suggesting different levels channel. Analysis distribution current amplitudes within levels. levels, often failing level. Applying fibres graded manner state, while reducing also both higher frequency reflect seen during complete activations. mdx/utrn−/− double knockout mice, Conductance variability may represent protein The results contribute muscle.