Modulation of serotonin induced currents by metals in mouse neuroblastoma cells

The effects of several metals on the serotonin receptor-channel complex were studied using mouse neuroblastoma N1E-115 cells which are known to be endowed with the 5-HT3 subclass of the receptor. The whole-cell patch damp technique was used to record currents induced by serotonin at a concentration of 3 mu M which was equivalent to the apparent dissociation constant. Methylmercury and mercuric chloride suppressed serotonin-induced currents irreversibly, with a 50% suppression being observed at concentrations of 3 mu M and 2 mu M, respectively. Lead and zinc suppressed the current with IC(50)s of 80 mu M and 50 mu M, respectively, and the effects of both metals were reversible after washing with metal-free solution. Lanthanum also suppressed the current with an IC50 of 10 mu M, and the effect was partially reversible. Cadmium and cobalt augmented serotonin-induced currents slightly but consistently at a concentration of 100 mu M, and the effect was reversible. Aluminum at 100 mu M had no effect on serotonin-induced currents. It was concluded that the 5-HT3 receptor is endowed with a unique property with respect to the actions of metals which is not shared by some other ligand-gated and voltage-gated ion channels.