Modification of NMDA responses by tri-n-butyltin in rat brain neurons.
1. 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. 2. 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 nM) reversibly caused a slight reduction in the inward currents and greatly increased the amplitude of the outward currents. 3. 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. 4. 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. 5. The NMDA-induced outward current was markedly inhibited by 5 mM tetraethylammonium chloride and 300 nM 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. 6. 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.
Kanemoto
Yumiko
Y
Cellular and System Physiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Ishibashi
Hitoshi
H
Matsuo
Shinichiro
S
Oyama
Yasuo
Y
Akaike
Norio
N
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004785:Environmental Pollutants / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D014220:Trialkyltin Compounds / Q000494:pharmacology*
D004785:Environmental Pollutants; D014220:Trialkyltin Compounds; C011559:tributyltin; D016202:N-Methylaspartate