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.
Department of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada.
A S
AS
Hazell
A M
AM
Hakim
M K
MK
Senterman
M J
MJ
Hogan
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