Decreased expression of maxi-K+ channel β1-subunit and altered vasoregulation in hypoxia

Background - Hypertension, a major cause of cardiovascular morbidity and mortality, can result from chronic hypoxia; however, the pathogenesis of this disorder is unknown. We hypothesized that downregulation of the maxi-K(+)channel beta(1)-subunit by hypoxia decreases the ability of these channels to hyperpolarize arterial smooth muscle cells, thus favoring vasoconstriction and hypertension. Methods and Results - Lowering O-2 tension produced a decrease of maxi-K+ beta(1)-subunit mRNA levels in rat (aortic and basilar) and human (mammary) arterial myocytes. This was paralleled by a reduction of the beta(1)-subunit protein level as determined by immunocytochemistry and flow cytometry. Exposure to hypoxia also produced a decrease of open probability, mean open time, and sensitivity to the xenoestrogen tamoxifen of single maxi-K(+)channels recorded from patch-clamped dispersed myocytes. The number of channels per patch and the single-channel conductance were not altered. The vasorelaxing force of maxi-K(+)channels was diminished in rat and human arterial rings exposed to low oxygen tension. Conclusions - These results indicate that a decrease of the maxi-K(+)channel beta(1)-subunit expression in arterial myocytes is a key factor in the vasomotor alterations induced by hypoxia.