TRP channels in skeletal muscle: gene expression, function and implications for disease

Abstract

Besides the well known voltage-gated Ca(2+) channels skeletal muscle fibres contain several non-voltage gated Ca(2+) conducting cation channels. They have been physiologically characterized as stretch activated, store operated and Ca(2+) leak channels. TRP channels are good candidates to account for these sarcolemmal channels and Ca(2+) influx pathways or at least contribute to the responsible macromolecular complexes. Several members of the TRPC, TRPV and TRPM subfamilies of TRP channels are expressed in skeletal muscle as shown by RT-PCR, Western blot and immunohistochemistry. The most prominent and consistently found are TRPC1, C3, C4 and C6, TRPV2 and V4 as well as TRPM4 and M7. However, the precise function of individual channels is largely unknown. Linking physiologically characterized channels of the muscle fibre membrane to TRP channel proteins has been a major challenge during the last years. It has been successful only in a few cases and is complicated by the fact that some channels have dual functions in cultured, immature muscle cells and adult fibres. The best characterized TRP channel in skeletal muscle is TRPC1, a small-conductance channel of the sarcolemma. It is needed for Ca(2+) homeostasis during sustained contractile muscle activity. In addition to certain physiological functions TRP channels seem to be involved in the pathomechanisms of muscle disorders. There is a broad body of evidence that dysregulation of Ca(2+) conducting channels plays a key role in the pathomechanism of Duchenne muscular dystrophy. Lack of the cytoskeletal protein dystrophin or δ-sarcoglycan, seems to disturb the function of one or several Ca(2+) channels of the muscle fibre membrane, leading to pathological dystrophic changes. Almost 10 different TRP channels have been detected in skeletal muscle. They seem to be involved in muscle development, Ca(2+) homeostasis, Ca(2+) signalling and in disease progression of certain muscle disorders. However, we are still at the beginning of understanding the impact of TRP channel functions in skeletal muscle.