Nervous system electrophysiology

L-Glutamate acts as an excitatory neurotransmitter at many synapses in the mammalian central nervous system. Electrophysiological measurements and the use of various selective agonists and antagonists indicate that different glutamate receptors co-exist on many neurons. 

An intermediate-duration oral MRL of 0.0007 mg/kg/day was derived for methyl parathion based on the observation of electrophysiological effects in the central and peripheral nervous systems of male rats exposed to methyl parathion through gavage administration of 0.22 mg/kg/day to the dams on days 5-15 of gestation and days 2-28 of lactation, followed by direct administration of the same dose to the male pups for 8 weeks. More marked effects occurred at the two higher doses, 0.44 and 0.88 mg/kg/day. The effects were dose-related, and were statistically significant at all three dose levels. The MRL was derived by dividing the LOAEL from this study (0.22 mg/kg/day) by an uncertainty factor of 300 (3 for a minimal LOAEL, 10 for extrapolation from animals to humans, and 10 for human variability). 

ATSDR has derived an intermediate-duration oral MRL of. 0007 mg/kg/day for methyl parathion based on a minimal LOAEL of 0.22 mg/kg/day for electrophysiological effects in the central and peripheral nervous systems in rats (Desi et al. 1998). 

Concentration and end point used for MRL derivation 0.22 mg/kg/day electrophysiological effects in the central and peripheral nervous systems... 

Recently, there has been a growth of interest in the development of in vitro methods for measuring toxic effects of chemicals on the central nervous system. One approach has been to conduct electrophysiological measurements on slices of the hippocampus and other brain tissues (Noraberg 2004, Kohling et al. 2005). An example of this approach is the extracellular recording of evoked potentials from neocortical slices of rodents and humans (Kohling et al. 2005). This method, which employs a three-dimensional microelectrode array, can demonstrate a loss of evoked potential after treatment of brain tissue with the neurotoxin trimethyltin. Apart from the potential of in vitro methods such as this as biomarkers, there is considerable interest in the use of them as alternative methods in the risk assessment of chemicals, a point that will be returned to in Section 16.8. 

Greene, RN and Haas, HE (1991) The electrophysiology of adenosine in the mammalian central nervous system. Prog. Neurobiol. 36 329-341. 

Central Nervous System. Behavioral pharmacology, learning and memory, specific ligand binding, neurochemistry, visual, auditory and/or electrophysiology examinations, and so on. 

There are a number of electrophysiological techniques available which can be used to detect and/or assess neurotoxicity. These techniques can be divided into two broad general categories those focused on central nervous system (CNS) function and those focused on peripheral nervous system function, (Seppalainer, 1975). 

The side-effects of cardiac glycosides are mostly caused by electrophysiological/neuronal phenomena. Gastro-intestinal adverse reactions are probably triggered by effects on the central nervous system. Various types of cardiac arrhythmias are caused by the influence of the drugs on nodal tissues in the heart. The risk of arrhythmia is strongly enhanced by low plasma potassium concentrations. 

Ophthalmologic problems, frequently involving impaired accomodation, photosensitivity, xanthopsia, etc. are also caused by electrophysiological phenomena, probably initiated in the central nervous system. 

Orexins increase transmitter release. This has been shown in electrophysiolog-ical studies for acetylcholine release in the myenteric plexus of the ileum and for GABA and glutamate release in a series of locations of the central nervous system (Table 5) in other words, presynaptic orexin receptors serve as heteroreceptors. Experiments on human tissue are so far lacking. In some of the experimental models listed in Table 5 orexin-A and orexin-B were studied and orexin-B was at least as... 

Chaput Y, de Montigny C. Effects of the 5-hydroxytryptamine receptor antagonist BMY 7378, on 5-hydroxytryptamine neurotransmission electrophysiological studies in the rat central nervous system. J Pharmacol Exp Ther 1988 246 359-370. 

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