Methylmercury acts at multiple sites to block hippocampal synaptic transmission.
To explore the mechanisms by which methylmercury (MeHg) blocks central synaptic transmission, intracellular recordings of action potentials and resting membrane potentials were made in CA1 neurons of rat hippocampal slices. At 4 to 100 microM, MeHg blocked action potentials in a concentration- and time-dependent manner. MeHg also depolarized Ca1 neuronal membranes. However, this effect occurred more slowly than block of action potentials because the resting membrane potentials remained unchanged when threshold stimulation-evoked action potentials were blocked. Thus, MeHg may initially alter the threshold level of neuronal membrane excitability and subsequently depolarize the membrane leading to block of synaptic transmission. To identify potential sites of action of MeHg, effects of MeHg on the responses of CA1 neurons to orthodromic stimulation of Schaffer collaterals, antidromic stimulation of the alveus, direct injection of current at cell soma and iontophoretic application of glutamate were compared. At 20 and 100 microM, MeHg blocked action potentials evoked by stimulation of Schaffer collaterals and by current injection at the cell soma at similar times. In contrast, action potentials evoked by stimulation of the alveus were blocked more rapidly by 100 microM MeHg than were action potentials evoked by current injection at CA1 neuronal soma. MeHg also blocked the responses of CA1 neurons to iontophoresis of glutamate, but time to block of these responses was slower than block of the corresponding orthodromically-evoked responses by stimulation of Schaffer collaterals. Compared to excitatory postsynaptic potentials, inhibitory postsynaptic potentials appeared to be more sensitive to MeHg, because block of inhibitory postsynaptic potentials occurred before block of excitatory postsynaptic potentials.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, USA.
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Yuan
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Atchison
D000818:Animals; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008767:Methylmercury Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects*
D008767:Methylmercury Compounds; C004925:methylmercuric chloride