JOURNAL ARTICLE

Modulation of inhibitory synaptic activity by a non-alpha4beta2, non-alpha7 subtype of nicotinic receptors in the substantia gelatinosa of adult rat spinal cord

Daisuke Takeda, Terumasa Nakatsuka, Roger Papke, Jianguo G Gu
Pain 2003, 101 (1): 13-23
12507696
The GABA/glycine-mediated inhibitory activity in the substantia gelatinosa (SG) of the spinal cord is critical in the control of nociceptive transmission. We examined whether and how SG inhibitory activity might be regulated by neuronal nicotinic receptors (nAChRs). Patch-clamp recordings were performed in SG neurons of spinal slice preparations from adult rats. We provided electrophysiological evidence that inhibitory presynaptic terminals in the SG expressed nAChRs and their activation resulted in large increases in the frequency of spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) in over 90% SG neurons tested. The enhancement of inhibitory activity was mediated by increases in the release of GABA/glycine, and direct Ca(2+) entry through SG presynaptic nAChRs appeared to be involved. Miniature IPSC frequency could be enhanced by the nAChR agonists nicotine or cytisine. Nicotine could still elicit large increases in mIPSC frequency in the presence of the alpha4beta2 nAChR antagonist dihydro-beta-erythroidine (5 microM) and the alpha7 nAChR-selective antagonist methyllycaconitine (40 nM). However, nicotine did not produce a significant enhancement of mIPSC frequency in the presence of the broad spectrum nAChR antagonist mecamylamine (5 microM). Nicotinic agonist-evoked whole-cell currents from SG neurons and the antagonist profiles also indicated the presence of a subtype of nAChRs, which were different from the major central nervous system nAChR subtypes, i.e. alpha4beta2* or alpha7 nAChRs. Together, our results suggest that a subtype of nAChR, possibly alpha3beta4* nAChR or a new nAChR type, is highly expressed at the inhibitory presynaptic terminals in SG of adult rats and play a role in the control of inhibitory activity in SG.

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