The TRP channels serving as chemical-to-electrical signal converter

Biology uses many signaling mechanisms. Among them, calcium and membrane potential are two prominent mediators for cellular signaling. Transient receptor potential (TRP) melastatin 4 and 5 (TRPM4 and TRPM5), two calcium-activated monovalent cation-selective ion channels, offer a direct linkage between these two signals. Their activities convert a rise in the intracellular calcium level, a chemical signal, into depolarization of membrane potential, an electrical signal. Interestingly, membrane depolarization can in turn alter the electrical driving force or membrane permeability for calcium entry; hence, it offers feedback mechanisms for regulating calcium signaling. By converging two powerful cellular signals, TRPM4 and TRPM5 can contribute to many fundamental biological processes including cardiovascular biology, immunology, insulin release, chemosensation, and others. Numerous mutations in TRPM4 are linked to human hereditary cardiac and skin diseases, whereas knocking out TRPM5 in mice abolishes the perception of sweet, umami, and bitter tastes. This review summarizes what is currently known about the signaling roles of these unique TRP channels and what remains mysterious.