Regional activation of L-type voltage-sensitive calcium channels in experimental thiamine deficiency

During pyrithiamine-induced thiamine deficiency (PTD), specific regions of the brain develop histological damage. The basis of this selective vulnerability is unknown but the mechanism may involve a glutamate-mediated excitotoxic process in affected structures, leading to alterations in membrane potential and disturbances in calcium homeostasis, In this study, we have examined the volume of distribution of [H-3]nimodipine, an L-type voltage-sensitive calcium channel (VSCC) antagonist, in the brain of the PTD rat. An increase in specific binding of [H-3]nimodipine was detected only in the posterior thalamus at the symptomatic stage, immediately following the loss of righting reflexes (P < 0.0001), 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. These 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 experimental thiamine deficiency. (C) 1998 Wiley-Liss, Inc.