Galantamine modulates the recovery from desensitization of nicotinic receptors in TE 671 cells

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Galantamine, an anti-cholinesterasic drug, is also known to allosterically potentiate the activation of nicotinic receptors. In this study, we investigated whether galantamine may additionally influence the nicotinic receptor recovery from desensitization. Whole-cell patch clamp experiments were performed on TE 671 cells, which natively express muscle-type nicotinic receptors, and desensitization was assessed based on a repetitive stimulation protocol. The desensitization process was studied at different ACh concentrations (10 - 100 mu M) alone or in the combination with galantamine (0.1 - 5 mu M). Both in the absence and in the presence of galantamine, the decay of the peak current elicited by agonist application within each stimulation train was well described by one simple exponential function. A comparative analysis of the time constants and the values of peak steady-state current obtained for each experimental condition showed: (i) an apparent non-linear desensitization with increasing ACh concentrations and (ii) a modulatory effect of galantamine on desensitization with an apparent non-linear dependency on the drug concentration. The different desensitization patterns observed for the various combinations of ACh/galantamine concentrations can be explained by assuming the existence of at least two functional populations of nicotinic receptors differing in which regards the desensitization behavior and their affinity for ACh and galantamine.
Original languageUnknown
Pages (from-to)4104-4118
JournalRomanian Biotechnological Letters
Issue number1
Publication statusPublished - 1 Jan 2009

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