TRPC channels: Integrators of multiple cellular signals

J. Soboloff, M. Spassova, T. Hewavitharana, L. P. He, P. Luncsford, W. Xu, K. Venkatachalam, D. Van Rossum, R. L. Patterson, D. L. Gill

Research output: Chapter in Book/Report/Conference proceedingChapter

37 Scopus citations

Abstract

TRPC channels are ubiquitously expressed among cell types and mediate signals in response to phospholipase C (PLC)-coupled receptors. TRPC channels function as integrators of multiple signals resulting from receptor-induced PLC activation, which catalyzes the breakdown of phosphatidylinositol 4,5-bisphosphate (PIP2) to produce inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 depletes Ca 2+ stores and TRPC3 channels can be activated by store-depletion. InsP3 also activates the InsP3 receptor, which may undergo direct interactions with the TRPC3 channel, perhaps mediating store-dependence. The other PLC product, DAG, has a direct non-PKC-dependent activating role on TRPC3 channels likely by direct binding. DAG also has profound effects on the TRPC3 channel through PKC. Thus PKC is a powerful inhibitor of most TRPC channels and DAG is a dual regulator of the TRPC3 channel. PLC-mediated DAG results in rapid channel opening followed later by a slower DAG-induced PKC-mediated deactivation of the channel. The decreased level of PIP2 from PLC activation also has an important modifying action on TRPC3 channels. Thus, the TRPC3 channel and PLCγ form an intermolecular PH domain that has high specificity for binding PIP2. This interaction allows the channel to be retained within the plasma membrane, a further operational control factor for TRPC3. As nonselective cation channels, TRPC channel opening results in the entry of both Na+ and Ca2+ ions. Thus, while they may mediate Ca2+ entry signals, TRPC channels are also powerful modifiers of membrane potential.

Original languageEnglish (US)
Title of host publicationTransient Receptor Potential (TRP) Channels
EditorsVeit Flockerzi, Bernd Nilius
Pages575-591
Number of pages17
DOIs
StatePublished - Dec 1 2007

Publication series

NameHandbook of Experimental Pharmacology
Volume179
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

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    Soboloff, J., Spassova, M., Hewavitharana, T., He, L. P., Luncsford, P., Xu, W., Venkatachalam, K., Van Rossum, D., Patterson, R. L., & Gill, D. L. (2007). TRPC channels: Integrators of multiple cellular signals. In V. Flockerzi, & B. Nilius (Eds.), Transient Receptor Potential (TRP) Channels (pp. 575-591). (Handbook of Experimental Pharmacology; Vol. 179). https://doi.org/10.1007/978-3-540-34891-7_34