Aim: 

Quaternary ammonium cholinesterase inhibitors (QChEIs), BW284c51, decamethonium (D) and edrophonium (E) have potent inhibitory actions on muscle-type acetylcholine receptors (nAChRs). So, we have now tested their effects on neuronal nAChR and other neuroreceptors.

Methods: 

Rat brain synaptosomal membranes were transplanted to Xenopus oocytes and currents elicited by GABA, kainate (KA) and ACh, either alone or co-applied with BW284c51, D or E, were recorded.

Results: 

After synaptosomal membrane injection, a₄b₂ nAChR, GABA_AR_, and KARs were functionally transplanted to the oocyte membrane. GABA_ARs, characterised by pentobarbital potentiation, bicuculline inhibition and outward rectification of the i/v relationship, were insensitive to 10-50 mM of any QChEI tested. Similarly, KARs, inhibited by DNQX (10 mM) and potentiated by cyclothiazide (25 mM), were affected by none of these QChEIs. Remarkably, a₄b₂ nAChRs, inhibited by either DHbE (50 mM) or 5-OH-indol (1 mM) and insensitive to either MLA (50 nM) or a-bungarotoxin (100 nM), were blocked by BW284c51 in a voltage-dependent way; besides, BW284c51 enhanced nAChR desensitisation, suggesting a complex modulation. D and E also inhibited a4b2nAChRs, but with smaller potency and without changing desensitisation.

Conclusion: 

QChEIs exert strong modulating effects on neuronal nAChRs, without affecting GABA_A or KARs.

This work was supported by DGICYT grant BFU2006-04781 (Spain).