Human cerebral arteries contain three Ca2+ channel subtypes with distinct physiological roles.

The conducted vasomotor response reflects electrical communication in the arterial wall and the distance signals spread is regulated by three factors including resident ion channels. This study defined the role of inward-rectifying K channels (K) in governing electrical communication along hamster cerebral arteries. Focal KCl application induced a vasoconstriction that conducted robustly, indicative of electrical communication among cells. Inhibiting dominant K conductances had no attenuating effect, the exception being Ba blockade of K. Electrophysiology and Q-PCR analysis of smooth muscle cells revealed a Ba-sensitive K current comprised of K2.1/2.2 subunits. This current was surprisingly small and when incorporated into a model, failed to account for the observed changes in conduction. We theorized a second population of K channels exist and consistent with this idea, a robust Ba-sensitive K2.1/2.2 current was observed in endothelial cells. When both K currents were incorporated into, and then inhibited in our model, conduction decay was substantive, aligning with experiments. Enhanced decay was ascribed to the rightward shift in membrane potential and the increased feedback arising from voltage-dependent-K channels. In summary, this study shows that two K populations work collaboratively to govern electrical communication and the spread of vasomotor responses along cerebral arteries.

Recent data suggest that T-type Ca 3.2 channels in arterial vascular smooth muscle cells (VSMCs) and pits structure of caveolae could contribute to elementary Ca signalling (Ca sparks) via ryanodine receptors (RyRs) to cause vasodilatation. While plausible, their precise involvement in igniting Ca sparks remains largely unexplored. The goal of this study was to elucidate the contribution of caveolar Ca 3.2 channels and their functional interaction with Ca 1.2 channels to trigger Ca sparks in VSMCs from mesenteric, tibial and cerebral arteries. We used tamoxifen-inducible smooth muscle-specific Ca 1.2 (SMAKO) mice and laser scanning confocal microscopy to assess Ca spark generation in VSMCs. Ni , Cd and methyl-β-cyclodextrin were used to inhibit Ca 3.2 channels, Ca 1.2 channels and caveolae, respectively. Ni (50 μmol L ) and methyl-β-cyclodextrin (10 mmol L ) decreased Ca spark frequency by ∼20-30% in mesenteric VSMCs in a non-additive manner, but failed to inhibit Ca sparks in tibial and cerebral artery VSMCs. Cd (200 μmol L ) suppressed Ca sparks in mesenteric arteries by ∼70-80%. A similar suppression of Ca sparks was seen in mesenteric artery VSMCs of SMAKO mice. The remaining Ca sparks were fully abolished by Ni or methyl-β-cyclodextrin. Our data demonstrate that Ca influx through Ca 1.2 channels is the primary means of triggering Ca sparks in murine arterial VSMCs. Ca 3.2 channels, localized to caveolae and tightly coupled to RyR, provide an additional Ca source for Ca spark generation in mesenteric, but not tibial and cerebral, arteries.