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.
Yin
X
X
Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Cui
W
W
Hu
G
G
Wang
H
H
D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002038:Bungarotoxins / Q000494:pharmacology; D002478:Cells, Cultured; D002794:Choline / Q000494:pharmacology; D004357:Drug Synergism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D018697:Nootropic Agents / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000502:physiology*; D013268:Stimulation, Chemical; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D002038:Bungarotoxins; C579165:Chrna7 protein, rat; D018721:Muscarinic Agonists; D018733:Nicotinic Antagonists; D018697:Nootropic Agents; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D010862:Pilocarpine; C054634:methyllycaconitine; D002794:Choline; D000157:Aconitine