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STIM, ORAI AND TRPC CHANNELS IN THE CONTROL OF CALCIUM ENTRY SIGNALS IN SMOOTH MUSCLE
Author(s) -
Wang Youjun,
Deng Xiaoxiang,
Hewavitharana Thamara,
Soboloff Jonathan,
Gill Donald L
Publication year - 2008
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2008.05018.x
Subject(s) - trpc , smooth muscle , chemistry , trpc5 , biophysics , microbiology and biotechnology , transient receptor potential channel , biology , endocrinology , receptor , biochemistry
SUMMARY1 Ca 2+ entry signals are crucial in the control of smooth muscle contraction. Smooth muscle cells are unusual in containing plasma membrane (PM) Ca 2+ entry channels that respond to voltage changes, receptor activation and Ca 2+ store depletion. 2 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. 3 Receptor activation results largely in Na + ion movement through TRPC6 channels, depolarization and subsequent activation of voltage‐dependent L‐type Ca 2+ channels. The TRPC6 channels also appear to be activated by mechanical stretch, resulting again in depolarization and L‐type Ca 2+ channel activation. Such a coupling may be crucial in mediating the myogenic tone response in vascular smooth muscle. 4 The emptying of stores mediated by inositol 1,4,5‐trisphosphate receptors triggers the endoplasmic reticulum (ER) Ca 2+ sensing protein st romal‐ i nteracting m olecule (STIM) 1 to translocate into defined ER–PM junctional areas in which coupling occurs to Orai proteins, which serve as highly Ca 2+ ‐selective low‐conductance Ca 2+ entry channels. 5 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 Ca 2+ channels. The STIM, Orai and TRPC channels represent highly promising new pharmacological targets through which such control may be induced.