Premium
Modification of NMDA responses by tri‐ n ‐butyltin in rat brain neurons
Author(s) -
Kanemoto Yumiko,
Ishibashi Hitoshi,
Matsuo Shinichiro,
Oyama Yasuo,
Akaike Norio
Publication year - 2002
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.0704707
Subject(s) - nmda receptor , chemistry , charybdotoxin , biophysics , tetraethylammonium chloride , electrophysiology , membrane potential , reversal potential , extracellular , tetraethylammonium , excitatory postsynaptic potential , channel blocker , patch clamp , neuroscience , receptor , biochemistry , biology , potassium , calcium , organic chemistry
The effects of the organotin, tri‐ n ‐butyltin (TBT), on N ‐methyl‐ D ‐aspartate (NMDA) induced membrane currents were investigated in order to evaluate possible neuronal actions of this toxic environmental pollutant. Experiments were conducted on neurons acutely dissociated from the rat dorsal motor nucleus of vagus (DMV) using the nystatin‐perforated patch clamp recording technique. In Mg 2+ ‐free physiological recording solutions, the application of NMDA to single DMV neurons held at a holding potential (V H ) of −40 mV evoked an inward current which rapidly reached a peak before declining to a steady‐state inward current. This was followed, immediately after NMDA washout, by a transient outward current. TBT (100 n M ) reversibly caused a slight reduction in the inward currents and greatly increased the amplitude of the outward currents. The reversal potential of the NMDA‐induced outward current in the presence of TBT was −86.7 mV, close to the theoretical K + equilibrium potential of −85.7 mV. The NMDA‐induced outward current was completely blocked when the K + in the internal solution was replaced with equimolar Cs + . Under these conditions, the NMDA induced current was more sustained and was unaffected by TBT. The NMDA‐induced outward current was markedly inhibited by 5 m M tetraethylammonium chloride and 300 n M charybdotoxin, and it was abolished by removal of extracellular Ca 2+ , suggesting that the outward current was due to the activation of Ca 2+ ‐activated K + channels by Ca 2+ influx through NMDA receptors. In conclusion, in rat DMV neurons, TBT potentiates the Ca 2+ ‐activated K + current induced by NMDA application without having any direct effects on the NMDA‐induced inward current. Given the significant role of NMDA receptor mediated excitation in various physiological and pathological processes, the modulation of this response by TBT may have an important influence on neuronal function.British Journal of Pharmacology (2002) 136 , 201–206; doi: 10.1038/sj.bjp.0704707