Diverse properties of store‐operated TRPC channels activated by protein kinase C in vascular myocytes

Abstract

In vascular smooth muscle, store-operated channels (SOCs) contribute to many physiological functions including vasoconstriction and cell growth and proliferation. In the present work we compared the properties of SOCs in freshly dispersed myocytes from rabbit coronary and mesenteric arteries and portal vein. Cyclopiazonic acid (CPA)-induced whole-cell SOC currents were sixfold greater at negative membrane potentials and displayed markedly different rectification properties and reversal potentials in coronary compared to mesenteric artery myocytes. Single channel studies showed that endothelin-1, CPA and the cell-permeant Ca 2+ chelator BAPTA-AM activated the same 2.6 pS SOC in coronary artery. In 1.5 mM [Ca 2+ ] o the unitary conductance of SOCs was significantly greater in coronary than in mesenteric artery. Moreover in 0 mM [Ca 2+ ] o the conductance of SOCs in coronary artery was unaltered whereas the conductance of SOCs in mesenteric artery was increased fourfold. In coronary artery SOCs were inhibited by the protein kinase C (PKC) inhibitor chelerythrine and activated by the phorbol ester phorbol 12,13-dibutyrate (PDBu), the diacylglycerol analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) and a catalytic subunit of PKC. These data infer an important role for PKC in activation of SOCs in coronary artery similar to mesenteric artery and portal vein. Anti-TRPC1 and -TRPC5 antibodies inhibited SOCs in coronary and mesenteric arteries and portal vein but anti-TRPC6 blocked SOCs only in coronary artery and anti-TRPC7 blocked SOCs only in portal vein. Immunoprecipitation showed associations between TRPC1 and TRPC5 in all preparations but between TRPC5 and TRPC6 only in coronary artery and between TRPC5 and TRPC7 only in portal vein. Finally, flufenamic acid increased SOC activity in coronary artery but inhibited SOCs in mesenteric artery and portal vein myocytes. These data provide strong evidence that vascular myocytes express diverse SOC isoforms, which are likely to be composed of different TRPC proteins and have different physiological functions.

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca2+ signals, and vasoconstriction in cerebral arteries

“…TRPC channels, including TRPC1, TRPC3, TRPC5, TRPC6, and TRPC7, are expressed in vascular smooth muscle cells and may contribute to I cat (2,12,28,36,39,40,54). In cerebral artery smooth muscle cells, TRPC3 channel knockdown attenuated endothelin-1-and IP 3 -induced [Ca 2ϩ ] i elevation and constriction, indicating that this isoform is a major contributor to the IP 3 R-induced I cat in this cell type (54).…”

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

“…In the case of the latter, entry of Ca 2+ through these L-type channel clusters does not directly activate RyR to produce sparks, but provides the necessary amount of Ca 2+ to charge up the ER and sensitize the RyR [52]. Another way of internal store reloading is achieved by the various isoforms of the transient receptor potential (TRP) ion channel family, activated directly by DAG [5,6].…”

“…The mechanism responsible for initiating Ca 2+ release depends on Ca 2+ sensitive SR calcium channels, the ryanodin receptor (RyR) 5 or the IP3 receptor (IP3R). Indeed, IP3R and RyR are highly sensitive to cytosolic Ca 2+ concentrations and when cytosolic Ca 2+ concentration ranges from nM to µM, they open up.…”

“…Alternatively, the calcium-dependent contractile response can be induced through the activation of specific membrane receptors coupled to phospholipase C (PLC) isoforms 3 . The various isoforms of transient receptor potential (TRP) ion channel family, particularly TRPC3, TRPC6 and TRPC7 possibly activated directly by diacyl glycerol (DAG), can also contribute to initial plasma membrane Ca 2+ influx and subsequent membrane depolarization [5][6][7][8]. Non-selective receptor-activated canonical TRPC6 channel, that conduct large sodium (Na 2+ ) currents was also suggested to contribute to membrane depolarization and subsequent Ltype channel activation [9,10].…”

Ionic Channels in the Therapy of Malignant Glioma

“…TRPC1 channels function in the regulation of neural stem cell proliferation, skeletal myoblast migration and differentiation, cell apoptosis and so on (Florio Pla et al, 2005;Louis et al, 2008;Bollimuntha et al, 2005). TRPC1 channels can be gated by receptor-operated pathway, store-operated pathway or even by mechanical stretch, depending on the cell types examined (Kim et al, 2003;Maroto et al, 2005;Saleh et al, 2008). Glioma-related TRPC1 channels are involved in glioma cell proliferation and cell migration.…”