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 investigat ed on cholinergic transmission in rat isolated atrial preparations whi ch had been incubated with [H-3]-choline to incorporate [H-3]acetylcho line into the cholinergic transmitter stores. The efflux of radioactiv ity evoked by electrical field stimulation of intrinsic parasympatheti c nerves (pulses at 5 Hz frequency in trains of 60 s duration) was tak en as an index of transmitter acetylcholine release. Stimulation-induc ed (S-I) efflux of radioactivity was virtually abolished by tetrodotox in (1 mu M) and by the removal of Ca2+ from the atrial superfusion flu id. The muscarinic cholinoceptor antagonist atropine (0.3 mu M) and th e alpha(2)-adrenoceptor antagonist idazoxan (0.3 mu M) each enhanced t he S-I efflux. Cromakalim (1 and 10 mu M) produced concentration-depen dent reductions in S-I efflux. Pinacidil (10 mu M) also reduced S-I ef flux, The inhibition of S-I afflux produced by cromakalim (10 mu M) an d pinacidil (10 mu M) was prevented by the ATP-sensitive potassium cha nnel 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 atria l parasympathetic nerves by activation of ATP-sensitive potassium chan nels. In addition, the finding that glibenclamide alone enhanced S-I e fflux in radiolabelled atrial preparations suggests that ATP-sensitive potassium channels are activated under the experimental conditions em ployed. Taken together, the findings indicate that, in rat atria, ATP- sensitive potassium channels may play a functional role in the regulat ion of transmitter acetylcholine release from parasympathetic choliner gic nerve terminals. (C) 1995 The Italian Pharmacological Society