Activation of store-operated channels by noradrenaline via protein kinase C in rabbit portal vein myocytes.
In the present study we have investigated the role of diacylglycerol (DAG) and protein kinase C (PKC) in mediating activation of Ca(2+)-permeable store-operated channels (SOCs) by noradrenaline in rabbit portal vein smooth muscle cells. With cell-attached recording, bath application of noradrenaline, 1-oleoyl-acetyl-sn-glycerol (OAG) and phorbol 12,13-dibutyrate (PDBu) evoked single channel currents. The biophysical properties of these channel currents were similar to those of the channel currents activated by depletion of internal Ca(2+) stores with cyclopiazonic acid (CPA). The activation of SOCs in cell-attached recording by noradrenaline, OAG, PDBu, CPA and the acetoxymethyl ester form of BAPTA (BAPTA-AM) was markedly inhibited by the PKC inhibitors chelerythrine and RO-31-8220. In isolated outside-out patches CPA did not evoke SOCs but noradrenaline stimulated SOC activity, which was reduced by about 90 % by PKC inhibitors. The addition of the serine/threonine phosphatase inhibitors calyculin A and microcystin also stimulated SOCs in isolated outside-out patches. It is concluded that in rabbit portal vein myocytes, noradrenaline activates SOCs via DAG and PKC, possibly by a store-independent mechanism. In addition in this cell type it appears that PKC and phosphorylation may play an important role in stimulating SOC activity in response to depletion of internal Ca(2+) stores by CPA and BAPTA-AM.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004075:Diglycerides / Q000378:metabolism; D004594:Electrophysiology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D011169:Portal Vein / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D011817:Rabbits
D000316:Adrenergic alpha-Agonists; D015220:Calcium Channels; D004075:Diglycerides; D011493:Protein Kinase C; D009638:Norepinephrine