Smooth muscle Ca(2+) -activated and voltage-gated K+ channels modulate conducted dilation in rat isolated small mesenteric arteries.

Abstract

To assess the influence of blocking smooth muscle large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels on the conducted dilation to ACh and isoproterenol. Rat mesenteric arteries were isolated with a bifurcation, triple-cannulated, pressurized and imaged using confocal microscopy. Phenylephrine was added to the superfusate to generate tone, and agonists perfused into a sidebranch to evoke local dilation and subsequent conducted dilation into the feed artery. Both ACh- and isoproterenol-stimulated local and conducted dilation with similar magnitudes of decay with distance along the feed artery (2000μm: ∼15% maximum dilation). The gap junction uncoupler carbenoxolone prevented both conducted dilation and intercellular spread of dye through gap junctions. IbTx, TEA or 4-AP, blockers of large conductance Ca(2+) -activated K+ channels and voltage-gated K+ channels, did not affect conducted dilation to either agonist. A combination of either IbTx or TEA with 4-AP markedly improved the extent of conducted dilation to both agonists (2000μm: >50% maximum dilation). The enhanced conducted dilation was reflected in the hyperpolarization to ACh (2000μm: Control, 4±1 mV, n = 3; TEA with 4-AP, 14±3mV, n=4), and was dependent on the endothelium. These data show that activated BK(Ca) and K(V) -channels serve to reduce the effectiveness of conducted dilation.