• Michiko Nakamura and Il-Sung Jang.
• Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.
• Eur. J. Pharmacol. 2010 Aug 25;640(1-3):178-84.

AbstractThe periaqueductal gray (PAG) is a major component of the descending pain inhibitory pathway, which is related to central analgesia. In the present study, we have investigated the possible roles of presynaptic nicotinic acetylcholine receptors in GABAergic transmission onto PAG neurons. In acutely isolated rat PAG neurons, GABAergic miniature inhibitory postsynaptic currents (mIPSCs) were recorded by use of a whole-cell patch clamp technique. Acetylcholine (30 microM) transiently increased both the frequency and amplitude of GABAergic mIPSCs. However, acetylcholine did not affect the GABA-induced membrane currents. This facilitatory action of acetylcholine disappeared in the presence of mecamylamine, a nonselective nicotinic receptor antagonist, and mimicked by nicotine, a nicotinic receptor agonist. The nicotine-induced increase in mIPSC frequency was completely blocked by dihydro-beta-erythroidine, a selective beta2-containing nicotinic receptor antagonist, but not methyllycaconitine or alpha-bungarotoxin, selective alpha7 nicotinic receptor antagonists. The results suggest that acetylcholine or nicotine acts presynaptic beta2-containing nicotinic receptors, presumably alpha4beta2 nicotinic receptors, to enhance spontaneous GABA release onto PAG neurons. The nicotine-induced increase in mIPSC frequency was completely occluded in the presence of Cd2+, a general voltage-dependent Ca2+ channels blocker, and in the absence of extracellular Ca2+ or Na+. The results suggest that presynaptic nicotinic receptors are less permeable to Ca2+, and that the activation of these receptors depolarizes GABAergic nerve terminals. In conclusion, presynaptic nicotinic receptors would temporally regulate the excitability of PAG neurons being not overexcited and eventually contribute to the cholinergic modulation of output from the PAG.Copyright (c) 2010 Elsevier B.V. All rights reserved.

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