1 November 2018
AP, action potential, SMC, smooth muscle cells, VGCC, voltage gated Ca2+ channels, MA, mesenteric artery, TEA, tetraethyl ammonium, 18β-GA, 18β-glycyrrhetinic acid, Intercellular Ca2+waves, Spreading vasoconstriction, Gap junctions, Mesenteric resistance artery
The role of vascular gap junctions in the conduction of intercellular Ca 2+ and vasoconstriction along small resistance arteries is not entirely understood. Some depolarizing agents trigger conducted vasoconstriction while others only evoke a local depolarization. Here we use a novel technique to investigate the temporal and spatial relationship between intercellular Ca 2+ signals generated by smooth muscle action potentials (APs) and vasoconstriction in mesenteric resistance arteries (MA). Pulses of exogenous KCl to depolarize the downstream end (T1) of a 3 mm long artery increased intracellular Ca 2+ associated with vasoconstriction. The spatial spread and amplitude of both depended on the duration of the pulse, with only a restricted non-conducting vasoconstriction to a 1 s pulse. While blocking smooth muscle cell (SMC) K + channels with TEA and activating L-type voltage-gated Ca 2+ channels (VGCCs) with BayK 8644 spread was dramatically facilitated, so the 1 s pulse evoked intercellular Ca 2+ waves and vasoconstriction that spread along an entire artery segment 3000 μm long. Ca 2+ waves spread as nifedipine-sensitive Ca 2+ spikes due to SMC action potentials, and evoked vasoconstriction. Both intercellular Ca 2+ and vasoconstriction spread at circa 3 mm s −1 and were independent of the endothelium. The spread but not the generation of Ca 2+ spikes was reversibly blocked by the gap junction inhibitor 18β-GA. Thus, smooth muscle gap junctions enable depolarization to spread along resistance arteries, and once regenerative Ca 2+-based APs occur, spread along the entire length of an artery followed by widespread vasoconstriction.