| First Author | Vasquez I | Year | 2012 |
| Journal | J Physiol | Volume | 590 |
| Issue | 23 | Pages | 6167-85 |
| PubMed ID | 22966155 | Mgi Jnum | J:203025 |
| Mgi Id | MGI:5523772 | Doi | 10.1113/jphysiol.2012.240044 |
| Citation | Vasquez I, et al. (2012) Partial opening and subconductance gating of mechanosensitive ion channels in dystrophic skeletal muscle. J Physiol 590(Pt 23):6167-85 |
| abstractText | 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 approximately 23 pS. Recordings from some patches, however, showed a smaller conductance channel of approximately 7-14 pS. Large and small conductance channels were detected in a single patch and showed serial, non-random gating, suggesting different opening levels of a single channel. Analysis of the distribution of current amplitudes within the open channel showed MS channels fluctuate between subconductance levels. MS channels in dystrophic muscle spend approximately 60% of the time at smaller subconductance levels, often failing to reach the fully open level. Applying pressure to the membrane of mdx fibres increases in a graded manner occupancy of the fully open state, while reducing occupancy of subconductance levels. Recordings also show partial openings of MS channels in both wild-type and mdx muscle that fail to reach the fully open state. Partial openings occur at a higher frequency in mdx muscle and reflect occupancy of subconductance levels seen during complete activations. In muscle from mdx/utrn(-/-) double knockout mice, MS channels also spend more time at subconductance levels than the fully open state. Conductance variability of MS channels may represent gating of a heteromeric protein composed of different channel subunits. The results also show that partial opening and prolonged burst duration are distinct mechanisms that contribute to excess Ca(2+) entry in dystrophic muscle. |
