Trimethyltin alters membrane properties of CA1 hippocampal neurons.
Trimethyltin produces pathological changes in the hippocampus, but the physiological mechanisms underlying its toxicity remain unclear. Intracellular recordings of CA1 neurons in rat hippocampal slices were conducted during bath application of 50 and 100 microM trimethyltin and 50 and 200 microM dimethyltin. Trimethyltin slowly depolarized the membrane potential without spontaneous spiking, and decreased input resistance and time constant. Trimethyltin decreased, in a dose-dependent manner, both the elicited action potential and the orthodromically-stimulated action potential amplitudes; increased the threshold current for both elicited and orthodromically-stimulated action potentials; and prolonged the duration of the orthodromic excitatory post-synaptic potential. These trimethyltin-induced effects were not readily reversed. On the other hand, dimethyltin at high concentrations only reduced the amplitude of the orthodromic action potential. Slice viability was compromised following exposure to trimethyltin, but not following dimethyltin. These data demonstrate that decreased membrane time constant and input resistance is an early and reliable indicator of the onset of trimethyltin-induced changes. The effects do not resemble those produced by excitotoxins, but rather share similarities with responses observed during slice hypoxia.
Harkins
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AB
Division of Life Sciences, University of Texas, San Antonio 78285.
Armstrong
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DL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects*; D009947:Organotin Compounds / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D014298:Trimethyltin Compounds / Q000633:toxicity*
D009947:Organotin Compounds; D014298:Trimethyltin Compounds; C039760:dimethyltin