TRP channels in normal and dystrophic skeletal muscle

TRP proteins constitute non-selective cation-permeable ion channels, most of which are permeable to Ca2+. In skeletal muscle, several isoforms of the TRPC (Canonical), TRPV (Vanilloid) and TRPM (Melastatin) subfamilies are expressed. In particular, TRPC1, C3 and C6, TRPV2 and V4, TRPM4 and TRPM7 have been consistently found in cultured myoblasts or in adult muscles. These channels seem to directly or indirectly respond to membrane stretch or to Ca2+ stores depletion; some isoforms might also constitute unregulated Ca2+ leak channels. Their function is largely unknown. TRPC1 and C3 have been involved in muscle development, in particular in myoblasts migration and differentiation. TRPC1 and V4 might allow a basal influx of Ca2+ at rest. Their lack has consequences on muscle fatigue. TRPV2 seems to be stretch-sensitive. It localizes mainly in intracellular pools at rest, and translocates to the plasma membrane upon IGF-1 stimulation. TRP channels seem to be involved in the pathophysiology of muscle disorders. In particular in Duchenne muscular dystrophy, the lack of the cytoskeletal protein dystrophin induces a disregulation of several ion channels leading to an abnormal influx of Ca2+. We discuss here, the possible involvement of TRP channels in this abnormal influx of Ca2+.

► TRP proteins constitute non-selective calcium-permeable channels. ► The most consistently found isoforms in skeletal muscle are TRPC1, C3, C6, TRPV2 and V4, TRPM4 and M7. ► In this review, we discuss the gating mechanisms of these TRP channels, their pharmacological profiles and their functions in normal muscle. ► Their possible involvement in Duchenne muscular dystrophy is also summarized.