Lidocaine effects on acetylcholine-elicited currents from mouse superior cervical ganglion neurons

Lidocaine is a commonly used local anaesthetic that, besides blocking voltage-dependent Na+ channels, has multiple inhibitory effects on muscle-type nicotinic acetylcholine (ACh) receptors (nAChRs). In the present study, we have investigated the effects of lidocaine on ACh-elicited currents (I(ACh)s) from cultured mouse superior cervical ganglion (SCG) neurons, which mainly express heteromeric alpha 3 beta 4 nAChRs. Neurons were voltage-clamped by using the perforated-patch method and I(ACh)s were elicited by fast application of ACh (100-300 mu M), either alone or in presence of lidocaine at different concentrations. I(ACh)s were reversibly blocked by lidocaine in a concentration-dependent way (IC50 = 41 mu M; n(H) close to I) and the inhibition was, at least partially, voltage-dependent, indicating an open-channel blockade. Besides, lidocaine blocked resting (closed) nAChRs, as evidenced by the increased inhibition caused by a 12 s lidocaine application just before its co-application with the agonist, and also enhanced I(ACh)s desensitisation, at concentrations close to the IC50. These results indicate that lidocaine has diverse inhibitory actions on neuronal heteromeric nAChRs resembling those previously reported for Torpedo (muscle-type) nAChRs (Alberola-Die et al., 2011). The similarity of lidocaine actions on different subtypes of heteromeric nAChRs differs with the specific effects of other compounds, restricted to particular subtypes of nAChRs. (C) 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.