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Activation of potassium channels by tempol in arterial smooth muscle cells from normotensive and deoxycorticosterone acetate-salt hypertensive rats.

Xu H, Jackson WF, Fink GD, Galligan JJ

Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA. xuhui2@msu.edu

Large-conductance Ca(2+)-activated potassium (BK) channels modulate vascular tone. Tempol, an O(2)(-) dismutase mimetic, causes vasodilation via activation of vascular BK channels. In this study, we investigated the mechanisms underlying tempol-induced activation of BK channels in mesenteric arterial (MA) myocytes from sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. In sham myocytes, whole-cell patch clamp studies showed that tempol enhanced peak outward currents (I(o)). This effect was larger in DOCA-salt myocytes. Tempol caused a leftward shift in the activation curve for I(o) in sham and DOCA-salt myocytes. In DOCA-salt myocytes, the peak I(o) at +80 mV did not differ from sham myocytes, but iberiotoxin (BK channel blocker) caused a larger reduction of I(o) in DOCA-salt compared with sham myocytes. Iberiotoxin but not 4-aminopyridine blocked the I(o) activated by tempol. Tiron, another O(2)(-) scavenger, had no effect on I(o). Using inside-out patches, we found that tempol caused a 4-fold increase in open probability (P(o)) of BK channels but did not change the mean channel open time in sham and DOCA-salt myocytes. Tempol did not change single channel conductance in sham or DOCA-salt myocytes. Western blot and immunocytochemical studies revealed that BK channel alpha-subunit expression was increased in DOCA-salt MA compared with sham MA. The data indicate that tempol directly activates BK channels by increasing channel P(o). We conclude that upregulation of the BK channel alpha-subunit protein and tempol-induced increases in BK channel P(o) contribute to the enhanced depressor response caused by tempol in DOCA-salt hypertensive rats.

Published 19 November 2006 in Hypertension, 48(6): 1080-7.
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