Ca 2+ Influx Through Vascular Smooth Muscle Cell Voltage‐Gated Ca 2+ Channels Increases Endothelial Cell Ca 2+ to Evoke Vasodilation

Global increases in vascular smooth muscle cell (SMC) intracellular Ca2+ typically lead to the formation of Ca2+-dependent cross-bridges between actin and myosin causing SMC contraction and vasoconstriction. We now show in skeletal muscle arterioles that Ca2+ influx through SMC voltage-gated Ca2+ channels (VGCCs) can activate a vasodilator signaling pathway in adjacent endothelial cells (ECs), so forming a bidirectional, voltage-dependent circuit between the SMCs and ECs, which provides negative feedback to supress vasoconstriction. Rat isolated cremaster arterioles from male Wistar rats were cannulated, pressurized and loaded with Oregon Green® 488 BAPTA-1 to image [Ca2+]i changes in either ECs and/or SMCs using laser scanning confocal microscopy. Direct activation of SMC VGCCs with BayK8644, or depolarization with raised K+, 4-AP or the α1-adrenoceptor agonist phenylephrine (PE), each indirectly stimulated local and propagating cell-wide Ca2+ events in the adjacent ECs. In freshly isolated EC tubes, whi...