Unliganded human mutant alpha 7 nicotinic receptors are modulated by Ca2+ and trace levels of Zn2+

A large body of evidence indicates that ligand-gated channels may open spontaneously, exhibiting a basal activity in the absence of the neurotransmitter. In the present work. we were interested in studying the Ca2+-induced modulation of the basal channel activity of unliganded human L248alpha7 receptors expressed in Xenopus oocytcs. While the basal channel activity was blocked by either the nicotinic antagonist methyllycaconitine or the superfusion With a Ca2+-free medium, it was enhanced by increasing external Ca2+ concentrations. External Ca2+ significantly influenced the channel properties lengthening the channel duration and reducing the channel conductance, in a dose dependent manner. Furthermore, the basal channel activity in standard medium was blocked by N,N,N',N'-tetrakis-2-pyrdylmethyl-ethylenediamine, the chelator of divalent cations with very high affinity for Zn2+, and was induced by Zn2+ when Ca2+ was present in the external medium. We conclude that basal activity of alpha7 mutant receptor-channels is caused by divalent cation contaminants present in the external medium, namely Zn2+; is positively modulated by the external Ca2+ and is inhibited when Ca2+ is absent front the medium. The patho-physiological consequences of these findings are discussed. (C) 2004 Elsevier Ltd. All rights reserved.