REGIONAL ACTIVATION OF L-TYPE VOLTAGE-SENSITIVE CALCIUM CHANNELS IN EXPERIMENTAL THIAMINE-DEFICIENCY

During pyrithiamine-induced thiamine deficiency (PTD), specific region s of the brain develop histological damage. The basis of this selectiv e vulnerability is unknown but the mechanism may involve a glutamate-m ediated excitotoxic process in affected structures, leading to alterat ions in membrane potential and disturbances in calcium homeostasis, In this study, we have examined the volume of distribution of [H-3]nimod ipine, an L-type voltage-sensitive calcium channel (VSCC) antagonist, in the brain of the PTD rat. An increase in specific binding of [H-3]n imodipine was detected only in the posterior thalamus at the symptomat ic stage, immediately following the loss of righting reflexes (P < 0.0 001), There was also an increase in nonspecific binding in the medial geniculate and inferior colliculi, Replenishment with thiamine at the symptomatic stage returned [H-3]nimodipine binding to normal levels. T hese findings provide evidence that depolarization and activation of L -type VSCCs occur in the posterior thalamus and may contribute to the appearance of histological lesions in this structure during experiment al thiamine deficiency. (C) 1998 Wiley-Liss, Inc.