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The Journal of Neuroscience, April 1, 1999, 19(7):2693-2705

Choline and Selective Antagonists Identify Two Subtypes of Nicotinic Acetylcholine Receptors that Modulate GABA Release from CA1 Interneurons in Rat Hippocampal Slices

Manickavasagom Alkondon1, Edna F. R. Pereira1, Howard M. Eisenberg2, and Edson X. Albuquerque1, 3

1 Department of Pharmacology and Experimental Therapeutics, 2 Department of Neurosurgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, and 3 Departamento de Farmacologia Básica e Clínica, ICB, CCS, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21944, Brazil

Neuronal nicotinic receptors (nAChR) are known to control transmitter release in the CNS. Thus, this study was aimed at exploring the diversity and localization of nAChRs present in CA1 interneurons in rat hippocampal slices. The use of a U-tube as the agonist delivery system was critical for the reliable detection of nicotinic responses induced by brief exposure of the neurons to ACh or to the alpha 7 nAChR-selective agonist choline. The present study demonstrated that CA1 interneurons, in addition to expressing functional alpha 7 nAChRs, also express functional alpha 4beta 2-like nAChRs and that activation of both receptors facilitates an action potential-dependent release of GABA. Depending on the experimental condition, one of the following nicotinic responses was recorded from the interneurons by means of the patch-clamp technique: a nicotinic whole-cell current, depolarization accompanied by action potentials, or GABA-mediated postsynaptic currents (PSCs). Responses mediated by alpha 7 nAChRs were short-lasting, whereas those mediated by alpha 4beta 2 nAChRs were long-lasting. Thus, phasic or tonic inhibition of CA1 interneurons may be achieved by selective activation of alpha 7 or alpha 4beta 2 nAChRs, respectively. It can also be suggested that synaptic levels of choline generated by hydrolysis of ACh in vivo may be sufficient to control the activity of the alpha 7 nAChRs. The finding that methyllycaconitine and dihydro-beta -erythroidine (antagonists of alpha 7 and alpha 4beta 2 nAChRs, respectively) increased the frequency and amplitude of GABAergic PSCs suggests that there is an intrinsic cholinergic activity that sustains a basal level of nAChR activity in these interneurons.

Key words: hippocampus; GABA; choline; methyllycaconitine; alpha -bungarotoxin; dihydro-beta -erythroidine


Copyright © 1999 Society for Neuroscience  0270-6474/99/1972693-13$05.00/0


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