Transient Receptor Potential Channels and Calcium Signaling

Transient receptor potential (TRP) cation channels play diverse roles in cellular Ca²⁺ signaling. First, as Ca²⁺-permeable channels that respond to a variety of stimuli, TRP channels can directly initiate cellular Ca²⁺ signals. Second, as nonselective cation channels, TRP channel activation leads to membrane depolarization, influencing Ca²⁺ influx via voltage-gated and store-operated Ca²⁺ channels. Finally, Ca²⁺ modulates the activity of most TRP channels, allowing them to function as molecular effectors downstream of intracellular Ca²⁺ signals. Whereas the TRP channel field has long been devoid of detailed channel structures, recent advances, particularly in cryo-electron microscopy-based structural approaches, have yielded a flurry of TRP channel structures, including members from all seven subfamilies. These structures, in conjunction with mutagenesis-based functional approaches, provided important new insights into the mechanisms whereby TRP channels permeate and sense Ca²⁺ These insights will be highly instrumental in the rational design of novel treatments for the multitude of TRP channel-related diseases.