The TRPC Class of Ion Channels: A Critical Review of Their Roles in Slow, Sustained Increases in Intracellular Ca2+ Concentrations

Abstract

The realization that there exists a multimembered family of cation channels with structural similarity to Drosophila's Trp channel emerged during the second half of the 1990s. In mammals, depending on the species, the TRP family counts 29 or 30 members which has been subdivided into 6 subfamilies on the basis of sequence similarity. TRP channels are nonselective monovalent cation channels, most of which also allow passage of Ca2+. Many members of each of these families, but not all, are involved in sensory signal transduction. The C-type (for canonical or classical) subfamily, differs from the other TRP subfamilies in that it fulfills two different types of function: membrane depolarization, resembling sensory transduction TRPs, and mediation of sustained increases in intracellular Ca2+. The mechanism(s) by which the C-class of TRP channels—the TRPCs—are activated is poorly understood and their role in mediating intracellular Ca2+ increases is being questioned. Both of these questions—mechanism of activation and participation in Ca2+ entry—are the topics of this review.