Premium
Blockade of glutamatergic and GABAergic receptor channels by trimethyltin chloride
Author(s) -
Krüger Katharina,
Diepgrond Victoria,
Ahnefeld Maria,
Wackerbeck Christina,
Madeja Michael,
Binding Norbert,
Musshoff Ulrich
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706083
Subject(s) - ionotropic effect , excitatory postsynaptic potential , glutamatergic , chemistry , inhibitory postsynaptic potential , gabaa receptor , glutamate receptor , neurotransmission , metabotropic receptor , gabaergic , nmda receptor , long term potentiation , neuroscience , pharmacology , receptor , biology , biochemistry
1 Organotin compounds such as trimethyltin chloride (TMT) are among the most toxic of the organometallics. As their main target for toxicity is the central nervous system, the aim of the present study was to investigate the effects of TMT on receptor channels involved in various processes of synaptic transmission. 2 The Xenopus oocyte expression system was chosen for direct assessment of TMT effects on voltage‐operated potassium channels and glutamatergic and GABAergic receptors, and hippocampal slices from rat brain for analyzing TMT effects on identified synaptic sites. 3 TMT was found to be ineffective, at 100 μ mol l −1 , against several potassium‐ and sodium‐operated ion channel functions as well as the metabotropic glutamate receptor. 4 The functions of the ionotropic glutamate and the GABA A receptor channels were inhibited by TMT in micromolar concentrations. Thus, at a maximum concentration of 100 μ mol l −1 , around 20–30% of the α ‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionic acid and GABA A receptor‐mediated ion currents and 35% of the N ‐methyl‐ D ‐aspartate receptor‐mediated ion currents were blocked. 5 In the hippocampal slice model, the inhibitory effects of TMT were much stronger than expected from the results on the ion channels. Bath application of TMT significantly reduced the amplitudes of evoked excitatory postsynaptic field potentials in a concentration‐dependent and nonreversible manner. 6 Induction of long‐term potentiation, recorded from the CA1 dendritic region, was inhibited by TMT and failed completely at a concentration of 10 μ mol l −1 . 7 In general, TMT affects the excitatory and inhibitory synaptic processes in a receptor specific manner and is able to disturb the activity within a neuronal network.British Journal of Pharmacology (2005) 144 , 283–292. doi: 10.1038/sj.bjp.0706083