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Ca 2+ Influx Through Vascular Smooth Muscle Cell Voltage‐Gated Ca 2+ Channels Increases Endothelial Cell Ca 2+ to Evoke Vasodilation
Author(s) -
Bagher Pooneh,
Garland Christopher,
Dora Kim
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.795.4
Subject(s) - chemistry , vasodilation , biophysics , biology , endocrinology
Global increases in vascular smooth muscle cell (SMC) intracellular Ca 2+ typically lead to the formation of Ca 2+ ‐dependent cross‐bridges between actin and myosin causing SMC contraction and vasoconstriction. We now show in skeletal muscle arterioles that Ca 2+ influx through SMC voltage‐gated Ca 2+ 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 [Ca 2+ ] 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 α 1 ‐adrenoceptor agonist phenylephrine (PE), each indirectly stimulated local and propagating cell‐wide Ca 2+ events in the adjacent ECs. In freshly isolated EC tubes, which lack influence from SMCs, direct and indirect activators of VGCCs did not alter EC [Ca 2+ ] i . These data demonstrate a SMC‐EC circuit that links VGCC‐dependent EC Ca 2+ activity to feedback regulation of vascular tone. Selective block of EC Ca 2+ ‐activated K + (K Ca ) channels markedly enhanced contraction to both direct (BayK8644) or indirect (PE) activators of VGCCs. Our data clearly demonstrate a link between global increases in SMC Ca 2+ with a secondary increase in EC Ca 2+ and activation of EC K Ca channels, to provide EC‐dependent feedback to supress vasoconstriction. This work was supported by the British Heart Foundation and the Wellcome Trust.