Unliganded human mutant α7 nicotinic receptors are modulated by Ca 2+ and trace levels of Zn 2+

Abstract

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 Ca 2+-induced modulation of the basal channel activity of unliganded human L248Tα7 receptors expressed in Xenopus oocytes. While the basal channel activity was blocked by either the nicotinic antagonist methyllycaconitine or the superfusion with a Ca 2+-free medium, it was enhanced by increasing external Ca 2+ concentrations. External Ca 2+ 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-pyridylmethyl-ethylenediamine, the chelator of divalent cations with very high affinity for Zn 2+, and was induced by Zn 2+ when Ca 2+ was present in the external medium. We conclude that basal activity of α7 mutant receptor-channels is caused by divalent cation contaminants present in the external medium, namely Zn 2+; is positively modulated by the external Ca 2+; and is inhibited when Ca 2+ is absent from the medium. The patho-physiological consequences of these findings are discussed.