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Effects of potassium channel openers and their antagonists on rat locus coeruleus neurones
Author(s) -
Finta E.P.,
Harms L.,
Sevcik J.,
Fischer H.D.,
Illes P.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13571.x
Subject(s) - cromakalim , glibenclamide , chemistry , tolbutamide , potassium channel , membrane potential , endocrinology , medicine , tetrodotoxin , potassium channel blocker , depolarization , kynurenic acid , hyperpolarization (physics) , apamin , pharmacology , antagonist , biology , biochemistry , stereochemistry , receptor , nuclear magnetic resonance spectroscopy , diabetes mellitus
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 μ m ) and cromakalim (100 μ m ) 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 μ m ) increased the firing rate, while glibenclamide (3 μ m ) only tended to do so. In addition, both compounds antagonized the effect of RO 31–6930 (10 μ m ). Neither glibenclamide (3 μ m ) nor tolbutamide (300 μ m ) altered the resting membrane potential. 3 Tetrodotoxin (0.5 μ m ) depressed the firing, but did not influence the inhibitory action of RO 31–6930 (10 μ m ). The excitatory amino acid antagonist, kynurenic acid (500 μ m ), 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 μ m ) hyperpolarized the cells and decreased their input resistance. This effect was not antagonized by glibenclamide (3 μ m ) or tolbutamide (300 μ m ). Ba 2+ (2 m m ), a blocker of both ATP‐sensitive and inwardly rectifying potassium channels, abolished the effects of RO 31–6930 (10 μ m ) and noradrenaline (100 μ m ). 6 These data suggest that K ATP channels are present on the noradrenergic LC neurones, but are not coupled to α 2 ‐adrenoceptors.