Mechanisms and significance of Ca(2+) entry through TRPC channels

The transient receptor potential (TRP) superfamily of plasma membrane cation channels has been recognized as a signaling hub in highly diverse settings of human physiopathology. In the past three decades of TRP research, attention was focused mainly on the channels Ca(2+) signaling function, albeit additional cellular functions, aside of providing a Ca(2+) entry pathway, have been identified. Our understanding of Ca(2+) signaling by TRP proteins has recently been advanced by a gain in high-resolution structure information on these pore complexes, and by the development of novel tools to investigate their role in spatiotemporal Ca(2+) handling. This review summarizes recent discoveries as well as remaining, unresolved aspects of the canonical subfamily of transient receptor potential channels (TRPC) research. We aim at a concise overview on current mechanistic concepts of Ca(2+) entry through- and Ca(2+) signaling by TRPC channels.