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Reproductive Sciences
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Large Conductance Ca2+—Activated K+ Channels Contribute to Vascular Function in Nonpregnant Human Uterine Arteries

Charles R. Rosenfeld, MD

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center, Department of Obstetrics and Gynecology University of Texas Southwestern Medical Center at Dallas, Texas, charles.rosenfeld{at}utsouthwestern.edu

R. Ann Word, MD

Department of Obstetrics and Gynecology University of Texas Southwestern Medical Center at Dallas, Texas

Kevin DeSpain, BS

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center

Xiao-tie Liu, MS, MD

Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Texas Southwestern Medical Center

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} -, β1- and β2-subunit protein. KCl and phenylephrine (PE, an {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). BK Ca are expressed in human UA and modulate vascular function by attenuating vasoconstrictor responses and contributing to nitric oxide-induced vasorelaxation.

Key Words: Nitric oxide,{alpha}-agonists • basal tone • myometrium • β1/β2-regulatory subunits.

Reproductive Sciences, Vol. 15, No. 7, 651-660 (2008)
DOI: 10.1177/1933719108319160
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Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
C. R. Rosenfeld, X.-t. Liu, and K. DeSpain
Pregnancy modifies the large conductance Ca2+-activated K+ channel and cGMP-dependent signaling pathway in uterine vascular smooth muscle
Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1878 - H1887.
[Abstract] [Full Text] [PDF]