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

36 Citations (Scopus)

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 publicationHandbook of Experimental Pharmacology
Pages575-591
Number of pages17
Volume179
DOIs
StatePublished - 2007
Externally publishedYes

Publication series

NameHandbook of Experimental Pharmacology
Volume179
ISSN (Print)01712004
ISSN (Electronic)18650325

Fingerprint

Diglycerides
Type C Phospholipases
TRPC Cation Channels
Chemical activation
Inositol 1,4,5-Trisphosphate
Cell membranes
Phosphatidylinositols
TRPC3 cation channel
Membrane Potentials
Cell Membrane
Ions
Membranes

Keywords

  • Calcium signaling
  • Store-operated channels
  • TRPC channels

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry
  • Medicine(all)

Cite this

Soboloff, J., Spassova, M., Hewavitharana, T., He, L. P., Luncsford, P., Xu, W., ... Gill, D. L. (2007). TRPC channels: Integrators of multiple cellular signals. In Handbook of Experimental Pharmacology (Vol. 179, pp. 575-591). (Handbook of Experimental Pharmacology; Vol. 179). https://doi.org/10.1007/978-3-540-34891-7_34

TRPC channels : Integrators of multiple cellular signals. / Soboloff, J.; Spassova, M.; Hewavitharana, T.; He, L. P.; Luncsford, P.; Xu, W.; Venkatachalam, K.; Van Rossum, D.; Patterson, R. L.; Gill, D. L.

Handbook of Experimental Pharmacology. Vol. 179 2007. p. 575-591 (Handbook of Experimental Pharmacology; Vol. 179).

Research output: Chapter in Book/Report/Conference proceedingChapter

Soboloff, J, Spassova, M, Hewavitharana, T, He, LP, Luncsford, P, Xu, W, Venkatachalam, K, Van Rossum, D, Patterson, RL & Gill, DL 2007, TRPC channels: Integrators of multiple cellular signals. in Handbook of Experimental Pharmacology. vol. 179, Handbook of Experimental Pharmacology, vol. 179, pp. 575-591. https://doi.org/10.1007/978-3-540-34891-7_34
Soboloff J, Spassova M, Hewavitharana T, He LP, Luncsford P, Xu W et al. TRPC channels: Integrators of multiple cellular signals. In Handbook of Experimental Pharmacology. Vol. 179. 2007. p. 575-591. (Handbook of Experimental Pharmacology). https://doi.org/10.1007/978-3-540-34891-7_34
Soboloff, J. ; Spassova, M. ; Hewavitharana, T. ; He, L. P. ; Luncsford, P. ; Xu, W. ; Venkatachalam, K. ; Van Rossum, D. ; Patterson, R. L. ; Gill, D. L. / TRPC channels : Integrators of multiple cellular signals. Handbook of Experimental Pharmacology. Vol. 179 2007. pp. 575-591 (Handbook of Experimental Pharmacology).
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