NS 1619 activates Ca2+-activated K+ currents in rat vas deferens.
The effects of NS 1619, a newly developed activator of large-conductance Ca2+-activated K+ channels, were investigated on single smooth muscle fibers dissociated enzymatically from rat vas deferens and on contractions of the epididymal half of vas deferens. K+ currents were recorded using whole-cell patch-clamp methods in near-physiological K+ solutions (5.4 mM extracellular K+/145 mM intracellular K+). When cell membrane voltage was stepped to test potentials (-60 to +60 mV) from a holding potential of -10 mV, NS 1619 increased the outwardly rectifying K+ current in a concentration-dependent manner. The increased portion of the K+ current by NS 1619 was totally abolished by charybdotoxin (100 nM) but not by glibenclamide (3 microM). NS 1619 reduced electrically stimulated contractile responses of rat vas deferens in a concentration-dependent manner, and charybdotoxin but not glibenclamide partially inhibited the effect of NS 1619. NS 1619 (50 microM) inhibited the noradrenaline-induced contraction. Charybdotoxin (100 nM) partially reduced the NS 1619-induced inhibition while glibenclamide (3 microM) had no effect. NS 1619 (10-100 microM) reduced the high K+-induced contractions in a noncompetitive manner. The present results indicate that NS 1619 activates charybdotoxin-sensitive Ca2+-activated K+ channels and probably inhibits Ca2+ influx. These two effects might account largely for the observed mechanical inhibition induced by NS 1619 in the epididymal half of isolated rat vas deferens.
Huang
Y
Y
Department of Physiology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, NT.
Lau
C W
CW
Ho
I H
IH
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D018999:Charybdotoxin / Q000494:pharmacology; D004558:Electric Stimulation; D004822:Epididymis / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D005110:Extracellular Space / Q000378:metabolism; D005905:Glyburide / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D001562:Benzimidazoles; D015221:Potassium Channels; D018999:Charybdotoxin; C086491:NS 1619; D011188:Potassium; D005905:Glyburide; D002118:Calcium; D009638:Norepinephrine