Large conductance Ca2+-activated K+ channels contribute to vascular function in nonpregnant human uterine arteries

Large conductance K+ channels (BKCa) are expressed in uterine artery (UA) smooth muscle from nonpregnant and pregnant sheep and contribute to the regulation of basal vascular tone and responses to estrogen and vasoconstrictors. To determine if BKCa are expressed in women and contribute to UA function, we collected UA from nonpregnant women (n = 31) at elective hysterectomy and analyzed for subunit protein, localization with immunohistochemistry, and function using endothelium-denuded rings. UA expresses BKCa alpha-,beta 1- and beta 2-subunit protein. KCl and phenylephrine (PE, and alpha(1)-agonist) caused dose-dependent vasoconstriction (P < .001), and UA precontracted with PE dose-dependently relaxed with sodium nitroprusside (SNP; P < .001). Tetraethylammonium chloride (TEA, 0.2-1.0 mM), a BKCa inhibitor, dose-dependently increased resting tone (P = .004; 28% +/- 5.3% with 1.0 mM), enhanced PE-induced (10(-6) M) vasoconstriction (P < .04), and attenuated SNP-induced relaxation at 1.0 mM (P = .02). BKCa are expressed in human UA and modulate vascular function by attenuating vasoconstrictor responses and contributing to nitric oxide-induced vasorelaxation.