Multiple activation mechanisms of store‐operated TRPC channels in smooth muscle cells

Abstract

Store-operated channels (SOCs) are plasma membrane Ca 2+ -permeable cation channels which are activated by agents that deplete intracellular Ca 2+ stores. In smooth muscle SOCs are involved in contraction, gene expression, cell growth and proliferation. Single channel recording has demonstrated that SOCs with different biophysical properties are expressed in smooth muscle indicating diverse molecular identities. Moreover it is apparent that several gating mechanisms including calmodulin, protein kinase C and lysophospholipids are involved in SOC activation. Evidence is accumulating that TRPC proteins are important components of SOCs in smooth muscle. More recently Orai and STIM proteins have been proposed to underlie the well-described calcium-release-activated current (I CRAC ) in non-excitable cells but at present there is little information on the role of Orai and STIM proteins in smooth muscle. In addition it is likely that different TRPC subunits coassemble as heterotetrameric structures to form smooth muscle SOCs. In this brief review we summarize the diverse properties and gating mechanisms of SOCs in smooth muscle. We propose that the heterogeneity of the properties of these conductances in smooth muscle results from the formation of heterotetrameric TRPC structures in different smooth muscle preparations.

The non-excitable smooth muscle: Calcium signaling and phenotypic switching during vascular disease

“…For example, all of the seven family members (TRPC1-7) are expressed in the vasculature [64,97] and studies examining the function of TRPC1 in VSMC suggest they are linked to Ca 2+ entry associated with intracellular Ca 2+ store depletion [7,13]. In no case has an expressed TRPC (which are nonselective) served to recapitulate the electrophysiological behavior of the archetypical Ca 2+ selective SOC channel, CRAC found in hematopoietic cells (lymphocytes, mast cells) [104].…”

Characterization of vasopressin-responsive collecting duct adenylyl cyclases in the mouse

“…While a host of other factors have been reported to stimulate collecting duct cAMP production, including aldosterone (46), PGI 2 (56), PGE 2 [via EP 4 (35)], ␤-adrenergic agonists (58,62), oxytocin (61), adenosine (26), angiotensin II (30), and glucagon (1,24), relatively (compared to AVP) few studies have examined these pathways or determined their physiological significance. Inhibitors of collecting duct cAMP production have almost exclusively been studied in the context of AVP stimulation; such negative regulators of AVP-stimulated cAMP accumulation include PGE 2 [likely via EP 3 (10)], dopamine (44), ATP (29,41), adenosine (42), endothelin-1 (ET-1) (36), and others.…”

“…A binding site responsible for calcium-dependent iPLA 2 regulation by CaM has been identified; displacement of CaM from iPLA 2 can accelerate iPLA 2 activity (3). iPLA 2 produces lysophospholipids that can open store-operated calcium channels, leading to inhibition of AC6 (4,48). Thus CaM inhibition might lead to reduced AC6 activity.…”

Essential role for STIM1/Orai1-mediated calcium influx in PDGF-induced smooth muscle migration

“…fibroblast growth factor] that typically couple to isoforms of PLC induces phosphatidylinositol 4,5-bisphosphate breakdown into two second messengers: inositol 1,4,5-trisphosphate (IP 3 ) and diacylglycerol. IP 3 causes Ca 2ϩ release through IP 3 receptors from the sarcoplasmic reticulum (SR) (9).…”