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 (KATP+ channels), which are abundant in the brain, has not yet been studied in long-term potentiation or long-term depression. We investigated whether KATP+ channel inhibition by the highly selective KATP+-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 μM) in submerged rat hippocampal slices. HMR-1372 (10 μM) 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 KATP+-channel inhibitor glibenclamide (20 μM) also ameliorated only strong long-term potentiation. Our data suggest that KATP+ channels are activated during or after induction of long-term potentiation and play a role in controlling synaptic excitability.