Modulatory Effects Of Desensitized α7 Nicotinic Receptors On Muscarinic Receptors

Nicotinic and muscarinic receptors, with the same endogenous ligand acetylcholine (ACh), are two types of cholinergic receptors, and belong to ionotropic receptor and GTP binding protein-coupled receptor superfamily respectively. They are one of the most important components of the cholinergic nervous system and mediate its function. Recent studies in our laboratory have indicated that the sensitivity of muscarinic receptors to their agonist can be increased by desensitized nicotinic receptors in both the central and the peripheral nervous systems. In the present study, whole-cell patch clamp recording from rat superior cervical ganglion neurons in culture was used to investigate the electrophysiological characteristics of a7-nAChRs and the influences of the desensitized a7-nAChRs on the activities of muscarinic receptors. An inward current was elicited through a7-nAChRs by rapid application of choline in the cultured neurons with an EC50 of about 11.8 mM. The choline-evoked current consisted of a fast and a slowly desensitizing component, both of which were sensitive to a-bungarotoxin and methyllycaconitine. The amplitudes of the choline-evoked currents recorded 0.5, 1, 2, and 3 min after the prolonged application of choline (10mM, 30s) were decreased to 25.3 ?9.2%, 45.9 ?11.8%, 66.3 ?14.5%, and 73.9 ?13.3% of their baseline levels, respectively; while the amplitudes of M-current (IM) recorded at the same times after theprolonged stimulation of choline were decreased to 52.7 ?17.4%, 63.9 ?4.2%, 70.9 + 2.8%, and 72.9 ?17.3% of their initial values respectively by application of pilocarpine (ImM, 5s) onto the soma of the neurons, and that was 79.8 ?13.7% before the desensitization of a7-nAChRs. Whereas, the desensitization of a7-nAChRs had no influence on the M-current, and the enhanced inhibition effects of muscarinic agonist on M-current after the desensitization of a7-nAChRs were removed in the presence of a-bungarotoxin and methyllycaconitine.Combined, it is reasonable to suggest that the activity of muscarinic receptors can be enhanced by the desensitized a7-nAChRs. This may be one of the important biological effects of the desensitized a7-nAChRs.