Circulation Research. 2003
Published online before print October 9, 2003, doi: 10.1161/01.RES.0000100068.43006.36
Published online before print October 9, 2003, doi: 10.1161/01.RES.0000100068.43006.36
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Submitted on September 3, 2003
Revised on September 25, 2003
Accepted on September 26, 2003
Downregulation of the BK Channel 
1 Subunit in Genetic Hypertension
Gregory C. Amberg and L. Fernando Santana *
From the Department of Physiology and Biophysics, University of Washington, Seattle, Wash.
* To whom correspondence should be addressed. E-mail: santana{at}u.washington.edu.
The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca2+ release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca2+ sparks) activate large-conductance, Ca2+-sensitive K+ (BK) channels. Ca2+ sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca2+ sparks and BK channel function in Wistar-Kyoto (WKY) rats with borderline hypertension and in spontaneously hypertensive rats (SHR), a widely used genetic model of severe hypertension. We found that the amplitude of spontaneous BK currents in WKY and SHR cells were smaller than in normotensive cells even though Ca2+ sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca2+ than normotensive cells. Our data indicate that decreased expression of the BK channel 
1 subunit underlies the lower Ca2+ sensitivity of BK channels in SHR and WKY myocytes. We conclude that the lower expression of the 1 subunit during genetic borderline and severe hypertension reduced BK channel activity by decreasing the sensitivity of these channels to physiological changes in Ca2+. These results support the view that changes in the molecular composition of BK channels may be a fundamental event contributing to the development of vascular dysfunction during hypertension.
Key words: Ca2+ sparks • ryanodine receptors • sarcoplasmic reticulum • iberiotoxin
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