Downregulation of the BK Channel 1 Subunit in Genetic Hypertension

نویسندگان

  • Gregory C. Amberg
  • L. Fernando Santana
چکیده

The molecular mechanisms underlying increased arterial tone during hypertension are unclear. In vascular smooth muscle, localized Ca release events through ryanodine-sensitive channels located in the sarcoplasmic reticulum (Ca sparks) activate large-conductance, Ca -sensitive K (BK) channels. Ca sparks and BK channels provide a negative feedback mechanism that hyperpolarizes smooth muscle and thereby opposes vasoconstriction. In this study, we examined Ca 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 Ca sparks were of similar magnitude. BK channels in WKY and SHR cells were less sensitive to physiological changes in intracellular Ca than normotensive cells. Our data indicate that decreased expression of the BK channel 1 subunit underlies the lower Ca 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 Ca . 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. (Circ Res. 2003;93:965-971.)

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تاریخ انتشار 2003