Modulation of GABAergic synaptic transmission by terminal nicotinic acetylcholine receptors in the central autonomic nucleus of the neonatal rat spinal cord

Abstract

Using patch clamp recordings from an in vitro spinal cord slice preparation of neonatal rats (9–15 days old), we characterized the GABAergic synaptic transmission in sympathetic preganglionic neurones (SPN) of the central autonomic nucleus (CA) of lamina X. Local applications of isoguvacine (100 μM), a selective agonist at GABA A receptors, induced in all cells tested a chloride current which was abolished by bicuculline, a competitive antagonist at GABA A receptors. In addition, 25% of the recorded cells displayed spontaneous tetrodotoxin-insensitive and bicuculline-sensitive chloride miniature inhibitory postsynaptic currents (mIPSCs). Acetylcholine (100 μM) increased the frequency of GABAergic mIPSCs without affecting their amplitudes or their kinetic properties indicating a presynaptic site of action. The presynaptic effect of ACh was restricted to GABAergic neurones synapsing onto sympathetic preganglionic neurones. The facilitatory effect of ACh was abolished in the absence of external calcium or in the presence of 100 μM cadmium added to the bath solution. Choline 10 mM, an agonist at α7 nicotinic acetylcholine receptors (nAChRs) or muscarine (10 μM), a muscarinic receptor agonist, did not reproduce the presynaptic effect of ACh. The presynaptic effect of ACh was blocked by 1 μM of dihydro-β-erythroidine (DHβE), an antagonist of non-α7 nAChRs but was insensitive to α7 nAChRs antagonists (strychnine, α-bungarotoxin and methyllycaconitine) or to the muscarinic receptor antagonist atropine (10 μM). It was concluded that SPNs of the central autonomic nucleus displayed a functional GABAergic transmission which is facilitated by terminal non α7 nAChRs.