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Stim, ORAI and TRPC channels in the control of calcium entry signals in smooth muscle.
Clin Exp Pharmacol Physiol. 2008 Sep; 35(9):1127-33.CE

Abstract

Ca2+ entry signals are crucial in the control of smooth muscle contraction. Smooth muscle cells are unusual in containing plasma membrane (PM) Ca2+ entry channels that respond to voltage changes, receptor activation and Ca2+ store depletion. Activation of these channel subtypes is highly coordinated. The TRPC6 channel, widely expressed in most smooth muscle cell types, is largely non-selective to cations and is activated by diacylglycerol arising from receptor-induced phosholipase C activation. Receptor activation results largely in Na+ ion movement through TRPC6 channels, depolarization and subsequent activation of voltage-dependent L-type Ca2+ channels. The TRPC6 channels also appear to be activated by mechanical stretch, resulting again in depolarization and L-type Ca2+ channel activation. Such a coupling may be crucial in mediating the myogenic tone response in vascular smooth muscle. The emptying of stores mediated by inositol 1,4,5-trisphosphate receptors triggers the endoplasmic reticulum (ER) Ca2+ sensing protein stromal-interacting molecule (STIM) 1 to translocate into defined ER-PM junctional areas in which coupling occurs to Orai proteins, which serve as highly Ca2+-selective low-conductance Ca2+ entry channels. These ER-PM junctional domains may serve as crucial sites of interaction and integration between the function of store-operated, receptor-operated and voltage-operated Ca2+ channels. The STIM, Orai and TRPC channels represent highly promising new pharmacological targets through which such control may be induced.

Authors+Show Affiliations

Department of Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

18782202

Citation

Wang, Youjun, et al. "Stim, ORAI and TRPC Channels in the Control of Calcium Entry Signals in Smooth Muscle." Clinical and Experimental Pharmacology & Physiology, vol. 35, no. 9, 2008, pp. 1127-33.
Wang Y, Deng X, Hewavitharana T, et al. Stim, ORAI and TRPC channels in the control of calcium entry signals in smooth muscle. Clin Exp Pharmacol Physiol. 2008;35(9):1127-33.
Wang, Y., Deng, X., Hewavitharana, T., Soboloff, J., & Gill, D. L. (2008). Stim, ORAI and TRPC channels in the control of calcium entry signals in smooth muscle. Clinical and Experimental Pharmacology & Physiology, 35(9), 1127-33. https://doi.org/10.1111/j.1440-1681.2008.05018.x
Wang Y, et al. Stim, ORAI and TRPC Channels in the Control of Calcium Entry Signals in Smooth Muscle. Clin Exp Pharmacol Physiol. 2008;35(9):1127-33. PubMed PMID: 18782202.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stim, ORAI and TRPC channels in the control of calcium entry signals in smooth muscle. AU - Wang,Youjun, AU - Deng,Xiaoxiang, AU - Hewavitharana,Thamara, AU - Soboloff,Jonathan, AU - Gill,Donald L, PY - 2008/9/11/pubmed PY - 2009/1/17/medline PY - 2008/9/11/entrez SP - 1127 EP - 33 JF - Clinical and experimental pharmacology & physiology JO - Clin Exp Pharmacol Physiol VL - 35 IS - 9 N2 - Ca2+ entry signals are crucial in the control of smooth muscle contraction. Smooth muscle cells are unusual in containing plasma membrane (PM) Ca2+ entry channels that respond to voltage changes, receptor activation and Ca2+ store depletion. Activation of these channel subtypes is highly coordinated. The TRPC6 channel, widely expressed in most smooth muscle cell types, is largely non-selective to cations and is activated by diacylglycerol arising from receptor-induced phosholipase C activation. Receptor activation results largely in Na+ ion movement through TRPC6 channels, depolarization and subsequent activation of voltage-dependent L-type Ca2+ channels. The TRPC6 channels also appear to be activated by mechanical stretch, resulting again in depolarization and L-type Ca2+ channel activation. Such a coupling may be crucial in mediating the myogenic tone response in vascular smooth muscle. The emptying of stores mediated by inositol 1,4,5-trisphosphate receptors triggers the endoplasmic reticulum (ER) Ca2+ sensing protein stromal-interacting molecule (STIM) 1 to translocate into defined ER-PM junctional areas in which coupling occurs to Orai proteins, which serve as highly Ca2+-selective low-conductance Ca2+ entry channels. These ER-PM junctional domains may serve as crucial sites of interaction and integration between the function of store-operated, receptor-operated and voltage-operated Ca2+ channels. The STIM, Orai and TRPC channels represent highly promising new pharmacological targets through which such control may be induced. SN - 1440-1681 UR - https://www.unboundmedicine.com/medline/citation/18782202/Stim_ORAI_and_TRPC_channels_in_the_control_of_calcium_entry_signals_in_smooth_muscle_ L2 - https://doi.org/10.1111/j.1440-1681.2008.05018.x DB - PRIME DP - Unbound Medicine ER -