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. In addition to conventional SA channels, some channels shift into a novel gating mode in which channels stay open for extended periods of time and are stretch-inactivated (SI). The shift in gating mode can occur slowly at the start of an experiment or more abruptly in response to strong pressure or voltage steps. SA and SI gating have similar energetic requirements, which likely reflect the energy required to deform the bilayer. The pharmacological properties of MS channels show similarities to other cation-selective channels. Highly charged pharmacological probes, such as lanthanide cations and aminoglycoside antibiotics, act by plugging the channel pore rather than interacting with the lipid bilayer.