An in vitro electrophysiological bioassay has been developed to quantitate dysfunctional effects in central nervous system (CNS) tissues arising from acute and/or chronic exposure to environmental neurotoxins. The focus of these studies is on carbon monoxide (CO), the related problem of hypoxia, and on methyl mercury. Using single-cell electrophysiological recording techniques in conjunction with a special environmental chamber, we are assessing the dose-response relationships of spontaneously active, mammalian cerebellar Purkinje cells to these neurotoxins. The cellular mechanisms underlying their effects are also being addressed. Both spectrophotometric and scanning electron microscopic techniques are also being employed to further delineate cause and effect relationships. Local p02, pH, and temperature are simultaneously monitored while controlled doses of gas and/or liquid phase insults are applied. The use of superfused divalent cation (Co ions) results in synaptic blockage, thus allowing us to study the bioenergetic mechanisms supporting neural membrane function and the effects of neurotoxins thereon. Our results so far have demonstrated not only the relative ease and speed with which this approach can assess CNS neurotoxicity, but also that CO seems to have a direct cellular effect over and above that due to tissue hypoxia per se.
NIH ExPorter
NIH ExPorter