Effects of monomethyltin and dimethyltin compounds on heterologously expressed neuronal ion channels (Xenopus oocytes) and synaptic transmission (hippocampal slices)

Kruger K, Hoing T, Bensch W, Diepgrond V, Ahnefeld M, Madeja M, Binding N, Musshoff U

Abstract

The aim of this study was to investigate the effects of monomethyltin trichloride (MMT) and dimethyltin dichloride (DMT) on various neuronal ion channels heterologously expressed in Xenopus oocytes and on synaptic transmission in hippocampal slices of young (14-21 days old) and adult (2-4 months old) rats. The Xenopus oocyte expression system was chosen to allow direct assessment of the effects of MMT and DMT both on glutamate receptors sensitive to AMPA and NMDA and on various voltage-operated potassium and sodium channels. Hippocampal slices were used to analyze the effects of MMT and DMT on synaptic potentials generated by the important excitatory Schaffer collateral-CAI synapse. In general, MMT and DMT were found to have no effect either on voltage-operated sodium and potassium channels or on the metabotropic glutamate receptor but they did differentially affect the functions of ionotropic glutamate receptors and glutamatergic synaptic transmission. MMT (100 mu M) significantly reduced NMDA-mediated ion currents by up to 32%, but had no effect on ion currents through AMPA receptors. In slices of adult rats, MMT had no effect on the amplitudes of evoked fEPSPs and brought about a 35% reduction in the UP amplitudes. In contrast, in slices of young rats MMT evoked a reversible 30% increase in the amplitudes of fEPSPs but had no effect on LTP induction. DMT (100 mu M) reduced ion currents through NMDA-receptor ion channels by up to 29% and those through AMPA-receptor ion channels by up to 7%. In hippocampal slices 100 mu M DMT reduced the amplitudes of fEPSPs (adults: 50%; young rats: 70%) and LTP (adults: 40%; young rats: 55%). Neither of the organotins affected the paired-pulse facilitation at this synapse, indicating that the organotins exert their effects at the postsynaptic site. The action of MMT and DMT may contribute to the organotin-induced impairment of behavior patterns in connection with learning and memory. (c) 2006 Elsevier Inc. All rights reserved.