Smooth muscle gap-junctions allow propagation of intercellular Ca ²⁺ waves and vasoconstriction due to Ca ²⁺ based action potentials in rat mesenteric resistance arteries

Graphical abstract

Highlights

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  In rat mesenteric resistance arteries (MA), smooth muscle (SMC) gap junctions enable intercellular Ca ²⁺ waves and vasoconstriction.

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  Simultaneous block of K ⁺ channels and activation of L-type VGCCs triggered SMC action potentials and propagating intercellular Ca ²⁺ waves.

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  Ca ²⁺ spread was spike-like in appearance, of constant speed at 2.6 ± 0.3 mm s ⁻¹ and associated with vasoconstriction spread at 2.5 ± 0.3 mm s ⁻¹.

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  The ability of arteries to spread intercellular Ca ²⁺ waves and phasic contractions was independent of the endothelium.

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  Propagation but not the generation of Ca ²⁺ spikes was reversibly inhibited by the gap junction blocker 18β-glycyrrhetinic acid (18β–GA).

Abstract

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.