K(+)-channel blockers restore synaptic plasticity in the neuromuscular junction of dunce, a Drosophila learning and memory mutant.
The effects of K(+)-channel blockers on synaptic transmission in dunce (dnc), a Drosophila learning and memory mutant, were investigated. Larvae dnc mutants lack facilitation and post-tetanic potentiation (PTP) at their motor end-plates; dnc mutants are also deficient in a form of phosphodiesterase, and exhibit abnormally high levels of cyclic adenosine 3',5'-monophosphate (cAMP). A two-microelectrode voltage-clamp was used to record end-plate currents and spontaneous end-plate currents from longitudinal ventrolateral third-instar larval muscle. The K(+)-channel blockers 3,4-diaminopyridine (3,4-DAP) and tetraethylammonium (TEA), at micromolar concentrations, caused a reversible decrease in end-plate current amplitudes both in wild-type and mutant end-plates. In the presence of blockers, a period of high-frequency stimulation (tetanus) of the nerve gave way to a transient increase in the end-plate currents of dnc mutants resembling facilitation and PTP in normal end-plates; 3,4-DAP and TEA also restored facilitation and PTP in normal end-plates after incubation with a non-hydrolysable analogue of cAMP (8Br-cAMP). It is suggested that a specific K+ conductance might be relevant to the lack of synaptic plasticity at the dnc neuromuscular synapses.
Centro de Estudios Cientificos de Santiago, Chile.
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Delgado
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Latorre
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Labarca
D015761:4-Aminopyridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000077770:Amifampridine; D000818:Animals; D004330:Drosophila / Q000235:genetics / Q000502:physiology; D007814:Larva; D007858:Learning; D008568:Memory; D009045:Motor Endplate / Q000187:drug effects / Q000502:physiology*; D009154:Mutation; D009473:Neuronal Plasticity / Q000187:drug effects*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*; D013997:Time Factors
D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D015124:8-Bromo Cyclic Adenosine Monophosphate; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D000077770:Amifampridine