The direct effect of carbon monoxide on KCa channels in vascular smooth muscle cells.
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 (KCa) 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 KCa 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 KCa channels in SMCs. Furthermore, the effect of CO on KCa channels was not mediated by cGMP or guanine nucleotide-binding proteins (G proteins, Gi/Go or Gs) in excised membrane patches. Our results suggest that the direct modulation of high-conductance KCa channels in vascular SMCs by CO may constitute a novel mechanism for the vascular effect of CO.
Wang
R
R
Departement de physiologie, Université de Montréal, C.P. 6128, Succ. Centre-ville, Montréal, Québec, Canada, H3C 3J7.
Wu
L
L
Wang
Z
Z
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002248:Carbon Monoxide / Q000633:toxicity*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D015221:Potassium Channels; D002248:Carbon Monoxide; D019204:GTP-Binding Proteins; D006152:Cyclic GMP; D002118:Calcium