In vitro assessment of neuromuscular toxicity.
This report has presented an overview of my approach to assessing neuromuscular toxicity using primarily in vitro techniques. Our current work on triethyltin toxicity exemplifies the use of these in vitro methodologies and the data they yield. Our neurophysiological and neurochemical experiments along with reports in the literature have directed our attention to several possible mechanisms for explaining the myopathic and neuropathic manifestation of TET intoxication. These mechanisms include (a) a compromise in the bioenergetic capacity of neurons and/or myofibers via disruption in mitochondrial function and (b) the direct effect of TET on the cell membrane and/or Na+-K+-ATPase. These hypotheses are currently being explored using additional biochemical and electrophysiological techniques in the isolated vascular perfused phrenic nerve-hemidiaphragm.
D000818:Animals; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D009130:Muscle, Smooth / Q000187:drug effects; D009468:Neuromuscular Diseases / Q000139:chemically induced*; D010830:Physostigmine / Q000633:toxicity; D051381:Rats; D013997:Time Factors; D014220:Trialkyltin Compounds / Q000633:toxicity
D014220:Trialkyltin Compounds; D010830:Physostigmine