RAPID DRUG APPLICATION RESOLVES 2 TYPES OF NICOTINIC RECEPTORS ON RATSYMPATHETIC-GANGLION CELLS

The properties of nicotinic acetylcholine receptors (AChRs) on culture d rat superior cervical ganglion (SCG) neurons were analysed. AChR ago nists [1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), cytisine] were applied to whole cells within 70ms. The desensitization rate of whole -cell currents during constant application of DMPP varied between neur ons. The time course of desensitization was fitted by double exponenti als with time constants k(fast), of between 0.35 and 0.55s, and k(slow ), of 3-5s. By exchanging intracellular chloride for caesium methanesu lphonate, the possibility of interference by a calcium-activated chlor ide current was excluded. In cells that exhibited a slowly desensitizi ng current during the application 20 mu M DMPP, equimolar cytisine ind uced a larger peak current compared to the response to DMPP, while in cells with rapidly desensitizing DMPP-induced currents the response to equimolar cytisine was smaller. The differences in desensitization ra tes and agonist potencies are due to different functional properties o f AChR subtypes, as indicated by currents recorded from outside-out pa tches upon rapid agonist application and removal (2ms each). The resul ts indicate the presence of two distinct AChR subtypes on SCG neurons: one with a fast and one with a slow activation/desensitization rate, but both with similar single-channel conductances. Slow activation/des ensitization was found to be associated with a high potency of cytisin e/low potency of DMPP. For AChRs with rapid activation/desensitization kinetics the agonist potencies were reversed.