TY - JOUR T1 - Involvement of Inositol 1,4,5-Trisphosphate Formation in the Voltage-Dependent Regulation of the Ca<sup>2+</sup> Concentration in Porcine Coronary Arterial Smooth Muscle Cells JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 486 LP - 496 DO - 10.1124/jpet.112.194233 VL - 342 IS - 2 AU - Hisao Yamamura AU - Susumu Ohya AU - Katsuhiko Muraki AU - Yuji Imaizumi Y1 - 2012/08/01 UR - http://jpet.aspetjournals.org/content/342/2/486.abstract N2 - The involvement of inositol 1,4,5-trisphosphate (IP3) formation in the voltage-dependent regulation of intracellular Ca2+ concentration ([Ca2+]i) was examined in smooth muscle cells of the porcine coronary artery. Slow ramp depolarization from −90 to 0 mV induced progressive [Ca2+]i increase. The slope was reduced or increased in the presence of Cd2+ or (±)-1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-[trifluoromethyl]-phenyl)pyridine-3-carboxlic acid methyl ester (Bay K 8644), respectively. The decrease in [Ca2+]i via the membrane hyperpolarization induced by K+ channel openers (levcromakalim and Evans blue) under current clamp was identical to that under voltage clamp. The step hyperpolarization from −40 to −80 mV reduced [Ca2+]i uniformly over the whole-cell area with a time constant of ∼10 s. The [Ca2+]i at either potential was unaffected by heparin, an inhibitor of IP3 receptors. Alternatively, [Ca2+]i rapidly increased in the peripheral regions by depolarization from −80 to 0 mV and stayed at that level (∼400 nM) during a 60-s pulse. When the pipette solution contained IP3 pathway blockers [heparin, 2-aminoethoxydiphenylborate, xestospongin C, or 1-[6-[((17β)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione (U73122)], the peak [Ca2+]i was unchanged, but the sustained [Ca2+]i was gradually reduced by ∼250 nM within 30 s. In the presence of Cd2+, a long depolarization period slightly increased the [Ca2+]i, which was lower than that in the presence of heparin alone. In coronary arterial myocytes, the sustained increase in the [Ca2+]i during depolarization was partly caused by the Ca2+ release mediated by the enhanced formation of IP3. The initial [Ca2+]i elevation triggered by the Ca2+ influx though voltage-dependent Ca2+ channels may be predominantly responsible for the activation of phospholipase C for IP3 formation. ER -