Nicotine facilitates glycine release in the rat spinal dorsal horn

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Abstract
1 Nicotinic effects on glycine release were investigated in slices of lumbar spinal cord using conventional whole-cell recordings. In most of the substantia gelatinosa (SG) neurons tested, nicotine increased the frequency of the glycinergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs). In a smaller proportion, nicotine evoked not only this same presynaptic response but also a postsynaptic response. 2 Nicotinic facilitation of glycinergic mIPSCs was investigated in mechanically dissociated SG neurons using nystatin-perforated patch recordings. Nicotine (3 × 10−6 to 10−5m) reversibly enhanced the frequency of glycinergic mIPSCs without altering their amplitudes, thus indicating that nicotine facilitates glycine release through a presynaptic mechanism. 3 Choline, a selective α7 subunit of nicotinic acetylcholine receptor (nAChR) agonist, had no effect on the mIPSC frequency while anatoxin A, a broad-spectrum agonist of nAChR, facilitated the mIPSC frequency. 4 α-Bungarotoxin, a selective α7 subunit antagonist, failed to block the nicotinic facilitatory action. Mecamylamine, a broad-spectrum nicotinic antagonist, reversibly inhibited nicotinic action. Dihydro-β-erythroidine, a selective antagonist of nAChRs containing α4-β2 subunits, completely blocked nicotinic action. 5 Ca2+-free but not Cd2+-containing bath solutions blocked nicotinic actions. 6 We therefore conclude that nicotine facilitates glycine release in the substantia gelatinosa of the spinal dorsal horn via specific nAChRs containing α4-β2 subunits. This action on a subset of presynaptic nAChRs may underlie nicotine's modulation of noxious signal transmission and provide a cellular mechanism for the analgesic function of nicotine.