alpha 7 nicotinic acetylcholine receptors and modulation of gabaergic synaptic transmission in the hippocampus

The present report provides new findings regarding modulation of gamma-amin obutyric acid (GABA) transmission by alpha 7 nicotinic receptor activity in CA1 interneurons of rat hippocampal slices. Recordings were obtained from tight-seal cell-attached patches of the CA1 interneurons, and agonists were delivered to the neurons via a modified U-tube. Application for 6 s of the alpha 7 nicotinic receptor-selective agonist choline (greater than or equa l to 1 mM) to all CA1 interneurons tested triggered action potentials that were detected as fast current transients. The activity triggered by choline terminated well before the end of the agonist pulse, was blocked by the al pha 7 nicotinic receptor antagonist methyllycaconitine (50 nM) and was conc entration dependent; the higher the concentration of choline the higher the frequency of events and the shorter the delay for detection of the first e vent. In 40% of the neurons tested, choline-triggered action potentials dec reased in amplitude progressively until no more events could be detected de spite the presence of the agonist. Primarily, this finding could be explain ed by Na+-channel inactivation associated with membrane depolarization indu ced by alpha 7 nicotinic receptor activation. In 60% of the neurons, the am plitude of choline-induced action potentials was sustained at the initial l evel, but again the activity did not last as long as the agonist pulse, in this case apparently because of agonist-induced receptor desensitization. T hese results altogether demonstrate that agonists interacting with alpha 7 nicotinic receptors, including the natural transmitter acetylcholine and it s metabolite choline, influence GABAergic transmission, not only by activat ing these receptors, but also by controlling the rate of Na+-channel inacti vation and/or by inducing receptor desensitization. (C) 2000 Elsevier Scien ce B.V. All rights reserved.