Dual role of calcium-activated potassium channels of high conductance: facilitator or limiter of NO-induced arterial relaxation?

AIM: Calcium-activated potassium channels of high conductance (BK(Ca) channels) are important contributors to vascular smooth muscle membrane potential and thus to vascular tone. BK(Ca) channels can promote vasodilation by facilitating vessel responses to NO. BK(Ca) channels may also serve as limiters of the anticontractile effect of NO. However, it is unclear whether BK(Ca) channels act simultaneously as facilitators and limiters in different vascular regions. Therefore, this study tested the hypothesis that BK(Ca) channels both facilitate and limit NO-induced vasorelaxation in multiple vessels. METHODS: Contractile responses of rat tail, saphenous, and left and right coronary arteries were studied using wire myography. RESULTS: The NO-donor SNP reduced contractile responses induced by low concentrations of methoxamine or serotonin, respectively, in all arteries tested, both in the absence and in the presence of iberiotoxin. This anticontractile effect of SNP was larger in the presence of iberiotoxin than in its absence, i.e., functionally active BK(Ca) channels limit the anticontractile effect of SNP. In contrast, the anticontractile effect of SNP at high concentrations of methoxamine or serotonin, respectively, in all arteries tested was smaller in the presence of iberiotoxin than in its absence, i.e., functionally active BK(Ca) channels facilitate the anticontractile effect of SNP. CONCLUSION: BK(Ca) channels simultaneously limit NO-induced vasodilation at lower levels of contractility but facilitate it at higher levels of contractility in multiple vascular beds. Therefore, BK(Ca) channels may play a dual role as facilitators and as limiters of the effect of NO, depending on the level of contractility.