Effects of cromakalim, pinacidil and glibenclamide on cholinergic transmission in rat isolated atria.
The effect of the potassium channel openers cromakalim and pinacidil, and the potassium channel blocking drug glibenclamide, were investigated on cholinergic transmission in rat isolated atrial preparations which had been incubated with [3H]-choline to incorporate [3H]-acetylcholine into the cholinergic transmitter stores. The efflux of radioactivity evoked by electrical field stimulation of intrinsic parasympathetic nerves (pulses at 5 Hz frequency in trains of 60 s duration) was taken as an index of transmitter acetylcholine release. Stimulation-induced (S-I) efflux of radioactivity was virtually abolished by tetrodotoxin (1 mu M) and by the removal of Ca2+ from the atrial superfusion fluid. The muscarinic cholinoceptor antagonist atropine (0.3 mu M) and the alpha2-adrenoceptor antagonist idazoxan (0.3 mu M) each enhanced the S-I efflux. Cromakalim (1 and 10 mu M) produced concentration-dependent reductions in S-I efflux. Pinacidil (10 mu M) also reduced S-I efflux. The inhibition of S-I efflux produced by cromakalim (10 mu M) and pinacidil (10 mu M) was prevented by the ATP-sensitive potassium channel blocking drug glibenclamide (1 mu M). Moreover, glibenclamide (1 mu M) alone enhanced S-I efflux. The findings suggest that cromakalim and pinacidil may inhibit transmitter acetylcholine release from atrial parasympathetic nerves by activation of ATP-sensitive potassium channels. In addition, the finding that glibenclamide alone enhanced S-I efflux in radiolabelled atrial preparations suggests that ATP-sensitive potassium channels are activated under the experimental conditions employed. Taken together, the findings indicate that, in rat atria, ATP-sensitive potassium channels may play a functional role in the regulation of transmitter acetylcholine release from parasympathetic cholinergic nerve terminals.
Fabiani
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ME
Department of Medical Laboratory Science, RMIT University, Melbourne, Australia.
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D000109:Acetylcholine / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D002799:Cholinergic Fibers / Q000187:drug effects*; D019806:Cromakalim; D005260:Female; D005905:Glyburide / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D006321:Heart / Q000294:innervation*; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008297:Male; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000494:pharmacology*
D001578:Benzopyrans; D006146:Guanidines; D007004:Hypoglycemic Agents; D015221:Potassium Channels; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D020110:Pinacidil; D000109:Acetylcholine; D005905:Glyburide