| First Author | Tan N | Year | 2014 |
| Journal | J Physiol | Volume | 592 |
| Issue | 15 | Pages | 3303-23 |
| PubMed ID | 24879867 | Mgi Jnum | J:243942 |
| Mgi Id | MGI:5912721 | Doi | 10.1113/jphysiol.2014.274332 |
| Citation | Tan N, et al. (2014) Utrophin regulates modal gating of mechanosensitive ion channels in dystrophic skeletal muscle. J Physiol 592(15):3303-23 |
| abstractText | 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. We find complex, gene dose-dependent effects of utrophin depletion in dystrophin-deficient mdx muscle: (1) increased MS channel open probability, (2) a shift of MS channel gating to larger pressures, (3) appearance of modal gating of MS channels and small conductance channels and (4) expression of large conductance MS channels. We suggest a physical model in which utrophin acts as a scaffolding protein that stabilizes lipid microdomains and clusters MS channel subunits. Depletion of utrophin disrupts domain composition in a manner that favours open channel area expansion, as well as allowing diffusion and aggregation of additional MS channel subunits. |
