Stretch-inactivated Channels in Skeletal Muscle

Excerpt

The mdx mouse, a deletion mutant that lacks full-length dystrophin, has been used to investigate the role of the cytoskeleton in mechanosensitive (MS) channel gating. Recordings of activity of single MS channels from mdx muscle show a novel gating mode with dramatically prolonged open times and stretch-inactivated gating. Compared with normal stretch-activated gating, stretch-inactivation occurs at lower pressures (P_1/2 = -13 and -36 mm Hg, respectively), but otherwise has a similar pressure-sensitivity as judged by the steepness of the relation between pressure and channel open probability. Stretch-inactivated channels can be induced in some patches by stretching the membrane or by voltage steps to positive potentials. The switch from stretch-activated to stretch-inactivated gating modes in mdx muscle is consistent with a model involving a change in hydrophobic mismatch between the channel protein and adjacent lipid bilayer. One function of dystrophin may be to organize the membrane into stable local microdomains containing specific phospholipids.