Aim To investigate the desensitization characteristics of neuronal ?4?2、?4?4 and ?7-nicotinic acetylcholine receptors heterologously expressed in the SH-EP1 cell line stimulated by prolonged of repetitive application of agonist.Methods The Whole cell recording configuration of patch-clamp technique was used to study the desensitization characteristics of ?4?2、?4?4 and ?7-nAChRs in cultured SH-EP1 cells three days after passage by rapid application of nicotine onto the soma of the cells.Results Inward currents were elicited by rapid application of agonist in all the three types of SH-EP1 cells in a concentration-dependent manner.?7-nAChRs desensitized the fastest and deepest in the three while ?4?4-nAChRs the slowest and lightest under prolonged stimulation.?4?2-nAChRs desensitized the fastest in the three under repetitive stimulation while ?4?4 and ?7-nAChRs didn't have obvious desensitization.Conclusion When stimulated by prolonged of repetitive application of agonist,neuronal ?4?2、?4?4 and ?7-nicotinic acetylcholine receptors had different desensitization characteristics,which is possibly associated with their roles in organophosphate poisoning inducing persistent stimulation of excessive accumulation of endogenous ACh and in nicotine addiction inducing repetitive stimulation of nicotine.