Effects of T-588, a newly synthesized cognitive enhancer, on hippocampal CA1 neurons in rat brain tissue slices.
The effects of a newly synthesized cognitive enhancer, (-)-R-alpha-[[2-(diethylamino) ethoxy] methyl] benzo [b] thiophene-5-methanol hydrochloride (T-588), on the membrane properties of hippocampal CA1 neurons were investigated in a rat brain slice preparation. T-588 produced a slow and long-lasting depolarization of CA1 neurons with an increase in membrane resistance; this action showed close similarity to that of acetylcholine (ACh). However, the action of T-588 was not affected by atropine, tetrodotoxin or DL-2-amino-5-phosphonovalerate, while the action of ACh was blocked by atropine. The estimated reversal potential of this T-588 effect was near -90 mV which is the reversal potential of potassium ions in CA1 neurons. In the whole-cell voltage-clamp study, T-588 produced a reversible block of the outward potassium current in CA1 neurons. T-588 did not block the afterhyperpolarization evoked by an intracellular current injection, while ACh suppressed it. These results suggest that T-588 has a direct effect on CA1 neurons independent of its cholinergic activity, resulting from blockade of a conductance carried predominantly by potassium ions.
Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
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Kimura
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Tamura
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Kurimoto
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Ono
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004048:Diethylamines / Q000494:pharmacology*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D016014:Linear Models; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018697:Nootropic Agents / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013779:Tetrodotoxin / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
D004048:Diethylamines; D018727:Muscarinic Antagonists; D018697:Nootropic Agents; D013876:Thiophenes; C082372:T 588; D013779:Tetrodotoxin; D015763:2-Amino-5-phosphonovalerate; D001285:Atropine; D000109:Acetylcholine