The ATP-regulated K+-channel inhibitor HMR-1372 affects synaptic plasticity in hippocampal slices.
Long-term potentiation (LTP) and long-term depression of synaptic transmission in the hippocampus are widely studied models of learning and memory processes. The role of ATP-regulated K+ channels (K(ATP)+ channels), which are abundant in the brain, has not yet been studied in long-term potentiation or long-term depression. We investigated whether K(ATP)+ channel inhibition by the highly selective K(ATP)+-channel blocker 1-[[5-[2-(5-tert-butyl-o-anisamido)ethyl]-2-methoxyphenyl]sulfonyl]-3-methylthiourea (HMR-1372), a novel putative class III antiarrhythmic, affects long-term potentiation or the long-term depression induced by 3,5-dihydroxyphenylglycine (30 microM) in submerged rat hippocampal slices. HMR-1372 (10 microM) did not affect basal synaptic transmission, paired pulse inhibition, long-term depression or long-term potentiation elicited by a weak (weak long-term potentiation) tetanus, but significantly amplified the long-term efficacy of long-term potentiation elicited by a strong tetanus (strong long-term potentiation). The K(ATP)+-channel inhibitor glibenclamide (20 microM) also ameliorated only strong long-term potentiation. Our data suggest that K(ATP)+ channels are activated during or after induction of long-term potentiation and play a role in controlling synaptic excitability.
Research Institute for Applied Neurosciences (FAN GmbH), Leipziger Str. 44, 39120, D-39120 Magdeburg, Germany. Ulrich.Schroeder@zenit-magdeburg.de
Ulrich H
UH
Schröder
Franz J
FJ
Hock
Klaus
K
Wirth
Heinrich C
HC
Englert
Klaus G
KG
Reymann
D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D000255:Adenosine Triphosphate