EFFECTS OF POTASSIUM CHANNEL OPENERS AND THEIR ANTAGONISTS ON RAT LOCUS-CERULEUS NEURONS

1 Intracellular recordings were obtained from a pontine slice preparation of the rat brain containing the locus coeruleus (LC). Two openers of ATP-sensitive potassium (K(ATP)) channels, RO 31-6930 (10 muM) and cromakalim (100 muM) decreased the spontaneous discharge of action potentials without altering their amplitude or duration. Neither compound changed the resting membrane potential. 2 Of two K(ATP) channel blockers, tolbutamide (300 muM) increased the firing rate, while glibenclamide (3 muM) only tended to do so. In addition, both compounds antagonized the effect of RO 31-6930 (10 muM). Neither glibenclamide (3 muM) nor tolbutamide (300 muM) altered the resting membrane potential. 3 Tetrodotoxin (0.5 muM) depressed the firing, but did not influence the inhibitory action of RO 31-6930 (10 muM). The excitatory amino acid antagonist, kynurenic acid (500 muM), did not change the spontaneous discharge of action potentials. 4 Small shifts (2-4 mV) of the membrane potential by hyper- or depolarizing current injections markedly decreased and increased the firing rate, respectively. 5 Noradrenaline (100 muM) hyperpolarized the cells and decreased their input resistance. This effect was not antagonized by glibenclamide (3 muM) or tolbutamide (300 muM). Ba2+ (2 mM), a blocker of both ATP-sensitive and inwardly rectifying potassium channels, abolished the effects of RO 31-6930 (10 muM) and noradrenaline (100 muM). 6 These data suggest that K(ATP) channels are present on the noradrenergic LC neurones, but are not coupled to alpha2-adrenoceptors.