STIM, ORAI AND TRPC CHANNELS IN THE CONTROL OF CALCIUM ENTRY SIGNALS IN SMOOTH MUSCLE

Authors: Wang, Youjun; Deng, Xiaoxiang; Hewavitharana, Thamara; Soboloff, Jonathan; Gill, Donald L

Source: Clinical and Experimental Pharmacology and Physiology, Volume 35, Number 9, September 2008 , pp. 1127-1133(7)

Publisher: Wiley-Blackwell

Abstract:

SUMMARY

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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.

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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.

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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.

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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.

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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.

Keywords: calcium channels; calcium signals; Orai; stromal-interacting molecule (STIM); TRPC channels

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1440-1681.2008.05018.x

Publication date: 2008-09-01

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