Excitatory and inhibitory synaptic transmission is differentially influenced by two ortho-substituted polychlorinated biphenyls in the hippocampal slice preparation.
Exposure to polychlorinated biphenyls impairs cognition and behavior in children. Two environmental PCBs 2,2',3,3',4,4',5-heptachlorobiphenyl (PCB170) and 2,2',3,5',6-pentachlorobiphenyl (PCB95) were examined in vitro for influences on synaptic transmission in rat hippocampal slices. Field excitatory postsynaptic potentials (fEPSPs) were recorded in the CA1 region using a multi-electrode array. Perfusion with PCB170 (10 nM) had no effect on fEPSP slope relative to baseline period, whereas (100 nM) initially enhanced then depressed fEPSP slope. Perfusion of PCB95 (10 or 100 nM) persistently enhanced fEPSP slope >200%, an effect that could be inhibited by dantrolene, a drug that attenuates ryanodine receptor signaling. Perfusion with picrotoxin (PTX) to block GABA neurotransmission resulted in a modest increase in fEPSP slope, whereas PTX+PCB170 (1-100 nM) persistently enhanced fEPSP slope in a dose dependent manner. fEPSP slope reached >250% of baseline period in the presence of PTX+100 nM PCB170, conditions that evoked marked epileptiform after-potential discharges. PCB95 and PCB170 were found to differentially influence the Ca(2+)-dependence of [(3)H]ryanodine-binding to hippocampal ryanodine receptors. Non-coplanar PCB congeners can differentially alter neurotransmission in a manner suggesting they can elicit imbalances between inhibitory and excitatory circuits within the hippocampus. Differential sensitization of ryanodine receptors by Ca(2+) appears to mediate, at least in part, hippocampal excitotoxicity by non-coplanar PCBs.
Kim
Kyung Ho
KH
Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, CA 95616, USA.
Inan
Salim Yalcin
SY
Berman
Robert F
RF
Pessah
Isaac N
IN
D000818:Animals; D003620:Dantrolene / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000633:toxicity; D006624:Hippocampus / Q000166:cytology*; D008297:Male; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010852:Picrotoxin / Q000633:toxicity; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D003620:Dantrolene; D004785:Environmental Pollutants; D010852:Picrotoxin; D011078:Polychlorinated Biphenyls; D019837:Ryanodine Receptor Calcium Release Channel; C032904:2,2',3,5',6-pentachlorobiphenyl; C541131:2,2',3,3',4,4',5-heptachlorobiphenyl