The direct effect of carbon monoxide on K_Ca channels in vascular smooth muscle cells

Abstract

 The vasorelaxation induced by carbon monoxide (CO) has been demonstrated previously. Both a guanosine cyclic monophosphate (cGMP) signalling pathway and cGMP-independent mechanisms have been proposed to be responsible for the vascular action of CO. A direct effect of CO on the activity of calcium-activated K (K_Ca) channels in vascular smooth muscle cells (SMCs) and the underlying mechanisms were investigated in the present study. It was found that CO hyperpolarized single SMCs isolated from rat tail arteries. The whole-cell outward K⁺ channel currents in vascular SMCs, but not in neuroblastoma cells, were enhanced by CO. Extracellularly or intracellularly applied CO increased the open probability of single high-conductance K_Ca channels concentration-dependently without affecting the single channel conductance. Although it did not increase the resting level of intracellular free calcium concentration, CO significantly enhanced the calcium sensitivity of single K_Ca channels in SMCs. Furthermore, the effect of CO on K_Ca channels was not mediated by cGMP or guanine nucleotide-binding proteins (G proteins, G_i/G_o or G_s) in excised membrane patches. Our results suggest that the direct modulation of high-conductance K_Ca channels in vascular SMCs by CO may constitute a novel mechanism for the vascular effect of CO.