Effects of potassium channel openers and their antagonists on rat locus coeruleus neurones

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Abstract
Intracellular recordings were obtained from a pontine slice preparation of the rat brain containing the locus coeruleus (LC). Two openers of ATP‐sensitive potassium (KATP) channels, RO 31–6930 (10 μm) and cromakalim (100 μm) decreased the spontaneous discharge of action potentials without altering their amplitude or duration. Neither compound changed the resting membrane potential. Of two KATP channel blockers, tolbutamide (300 μm) increased the firing rate, while glibenclamide (3 μm) only tended to do so. In addition, both compounds antagonized the effect of RO 31–6930 (10 μm). Neither glibenclamide (3 μm) nor tolbutamide (300 μm) altered the resting membrane potential. Tetrodotoxin (0.5 μm) depressed the firing, but did not influence the inhibitory action of RO 31–6930 (10 μm). The excitatory amino acid antagonist, kynurenic acid (500 μm), did not change the spontaneous discharge of action potentials. Small shifts (2–4 mV) of the membrane potential by hyper‐ or depolarizing current injections markedly decreased and increased the firing rate, respectively. Noradrenaline (100 μm) hyperpolarized the cells and decreased their input resistance. This effect was not antagonized by glibenclamide (3 μm) or tolbutamide (300 μm). Ba2+ (2 mm), a blocker of both ATP‐sensitive and inwardly rectifying potassium channels, abolished the effects of RO 31–6930 (10 μm) and noradrenaline (100 μm). These data suggest that KATP channels are present on the noradrenergic LC neurones, but are not coupled to α2‐adrenoceptors.