Desensitization of alpha7 nicotinic receptors potentiated the inhibitory effect on M-current induced by stimulation of muscarinic receptors in rat superior cervical ganglion neurons.

Whole-cell patch-clamp recording from rat superior cervical ganglion neurons in culture was used to investigate the modulatory effect of desensitized alpha7-nAChRs on mAChRs. An inward alpha-bungarotoxin and methyllycaconitine sensitive current was elicited by rapid application of choline, which consisted of a fast and a slow desensitizing component. The amplitude of choline-evoked currents recorded 0.5, 1, 2, and 3 min after the prolonged application of choline (10 mM, 30 s) decreased to 25.3 +/- 9.2%, 45.9 +/- 11.8%, 66.3 +/- 14.5%, and 73.9 +/- 13.3% of their baseline levels, respectively. The amplitudes of M-currents, recorded at the same time intervals after the similar prolonged stimulation with choline, were decreased to 52.7 +/- 17.4%, 63.9 +/- 4.2%, 70.9 +/- 2.8%, and 72.9 +/- 17.3% of initial values respectively by focal application of pilocarpine (1 mM, 5 s) onto the soma of neurons. By contrast, before the desensitization of alpha7-nAChRs, M-currents were only decreased to 79.8 +/- 13.7% of baseline levels by pilocarpine (1 mM, 5 s). Whereas the desensitization of alpha7-nAChRs had no direct effects on M-currents, and the facilitated effects on muscarinic agonists on the M-currents induced by desensitized alpha7-nAChRs, were removed in the presence of alpha-bungarotoxin and methyllycaconitine. These results indicated that desensitization of alpha7-nAChRs could potentiate the inhibitory effect on M-current by stimulation of mAChRs with their agonist.