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(Circulation. 2005;112:1309-1315.)
© 2005 American Heart Association, Inc.

Molecular Cardiology

Decreased Expression of Maxi-K⁺ Channel ß₁-Subunit and Altered Vasoregulation in Hypoxia

Javier Navarro-Antolín, MD, PhD; Konstantin L. Levitsky, PhD; Eva Calderón, MS; Antonio Ordóñez, MD, PhD; José López-Barneo, MD, PhD

From the Laboratorio de Investigaciones Biomédicas (J.N.-A., K.L.L., J.L.-B.) and Unidad de Cirugía y Trasplante Cardíaco (E.C., A.O.), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain.

Correspondence to José López-Barneo, Laboratorio de Investigaciones Biomédicas, Edificio de Laboratorios, 2^a planta, Hospital Universitario Virgen del Rocío, Avenida Manuel Siurot s/n, E-41013 Sevilla, Spain. E-mail jose.l.barneo.sspa{at}juntadeandalucia.es

Received December 13, 2004; revision received May 6, 2005; accepted May 25, 2005.

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 ß₁-subunit by hypoxia decreases the ability of these channels to hyperpolarize arterial smooth muscle cells, thus favoring vasoconstriction and hypertension.

Methods and Results— Lowering O₂ tension produced a decrease of maxi-K⁺ ß₁-subunit mRNA levels in rat (aortic and basilar) and human (mammary) arterial myocytes. This was paralleled by a reduction of the ß₁-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 ß₁-subunit expression in arterial myocytes is a key factor in the vasomotor alterations induced by hypoxia.

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