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

An absence of utrophin in muscle from mdx mice prolongs the open time of single mechanosensitive channels. On a time scale much longer than the duration of individual channel activations, genetic depletion of utrophin produces low frequency oscillations of channel open probability. Oscillatory channel opening occurred in the dystrophin/utrophin mutants, but was absent in wild-type and mdx fibers.

Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic skeletal muscle.

Dystrophin is a large, submembrane cytoskeletal protein, absence of which causes Duchenne muscular dystrophy. Utrophin is a dystrophin homologue found in both muscle and brain whose physiological function is unknown. Recordings of single-channel activity were made from membrane patches on skeletal muscle from mdx, mdx/utrn(+/-) heterozygotes and mdx/utrn(-/-) double knockout mice to investigate the role of these cytoskeletal proteins in mechanosensitive (MS) channel gating.

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

We recorded the activity of single mechanosensitive (MS) ion channels in skeletal muscle from the mdx mouse, a deletion mutant that lacks the cytoskeletal protein, dystrophin. Experiments were designed to examine the influence of dystrophin, a major component of skeletal muscle costameres, on the behaviour of single MS channels. In the majority of recordings from cell-attached patches, MS channels have a conductance of ∼23 pS.

Evidence TRPV4 contributes to mechanosensitive ion channels in mouse skeletal muscle fibers.

We recorded the activity of single mechanosensitive (MS) ion channels from membrane patches on single muscle fibers isolated from mice. We investigated the actions of various TRP (transient receptor potential) channel blockers on MS channel activity. 2-aminoethoxydiphenyl borate (2-APB) neither inhibited nor facilitated single channel activity at submillimolar concentrations.

Mechanosensitive ion channels in dystrophic muscle.

Mechanosensitive (MS) ion channels are expressed abundantly in skeletal muscle at all stages of development. In wild-type muscle, MS channels show primarily stretch-activated (SA) gating. In dystrophic myotubes from the mdx mouse, a loss-of-function mutant that lacks dystrophin, there are two types of MS channels.