Modulation of adrenergic responses of human vas deferens by K+ channel inhibitors.


OBJECTIVES The present study was designed to evaluate the role of K(+) channels in the adrenergic responses of human vas deferens as well as the intervention of dihydropyridine-sensitive Ca(2+) channels on modulation of adrenergic responses by K(+) channel inhibitors. METHODS Ring segments of the epididymal part of the vas deferens were taken from 32 elective vasectomies and mounted in organ baths for isometric recording of tension. We then studied the effects of K(+) channel blockers on neurogenic and norepinephrine-induced contractile responses. RESULTS Addition of tetraethylammonium (TEA, 10(-3) M), a nonspecific K(+) channel blocker, or charybdotoxin (10(-7) M), a nonselective inhibitor of large- and intermediate-conductance Ca(2+)-activated K(+) channel, increased the contractile responses to norepinephrine and electrical field stimulation-induced contractions (P < .01), whereas iberiotoxin (10(-7) M), a selective blocker of large-conductance Ca(2+)-activated K(+) channels, apamin (10(-6) M), a blocker of small-conductance Ca(2+)-activated K(+) channels, or glibenclamide (10(-5) M), an inhibitor of ATP-sensitive K(+) channels, were without effect. TEA- and charybdotoxin-induced potentiation of contractions elicited by electrical field stimulation and norepinephrine was blocked by L-type Ca(2+) channel blocker nifedipine (10(-6) M). CONCLUSIONS The results suggest that charybdotoxin-sensitive, but iberiotoxin-insensitive, K(+) channels are activated by stimulation with norepinephrine and electrical field stimulation to counteract the adrenergic-induced contractions of human vas deferens. Thus, inhibition of these channels increases significantly the contraction, an effect that appears to be mediated by an increase in Ca(2+) entry through L-type voltage-dependent Ca(2+) channels.


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