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Am J Physiol Cell Physiol 273: C45-C56, 1997;
0363-6143/97 $5.00
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AJP - Cell Physiology, Vol 273, Issue 1 C45-C56, Copyright © 1997 by American Physiological Society

ARTICLES

Inhibition of maxi-K currents in ferret portal vein smooth muscle cells by the antifungal clotrimazole

A. R. Rittenhouse, C. Parker, C. Brugnara, K. G. Morgan and S. L. Alper
Molecular Medicine Unit, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.

The antifungal agent clotrimazole (CLT) is a potent small-molecule inhibitor of Ca-activated K (KCa) currents of intermediate conductance in murine erythroleukemia cells. This study demonstrates that CLT also inhibits large-conductance KCa currents (maxi-K currents) in acutely dissociated vascular smooth muscle (VSM) cells of ferret portal vein. The magnitude of block of a component of the whole cell K current by CLT was sensitive to test potential. CLT inhibited unitary maxi-K currents in outside-out patches, apparently by decreasing the mean open time. A metabolite of CLT lacking an imidazole ring also inhibited K currents. In contrast, the antifungal drug ketoconazole increased these same currents. Thus the inhibitory action of CLT appears to be due to a direct interaction with the channel protein rather than to imidazole block of cytochrome P-450 activity. Consistent with inhibition of maxi-K currents by CLT, superfusion of strips of portal vein VSM with CLT enhanced isometric tension and spontaneous rate of contraction, suggesting that CLT modulation of maxi-K currents may alter vasomotor functioning.


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