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 [3H]nimodipine, an L-type voltage-sensitive calcium channel (VSCC) antagonist, in the brain of the PTD rat. An increase in specific binding of [3H]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 [3H]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.
Hazell
A S
AS
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
Hakim
A M
AM
Senterman
M K
MK
Hogan
M J
MJ
D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D004594:Electrophysiology; D004789:Enzyme Activation / Q000502:physiology; D008297:Male; D009553:Nimodipine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013832:Thiamine Deficiency / Q000378:metabolism* / Q000473:pathology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D009553:Nimodipine