What is the role of intracellular calcium buffering in the pathophysiology of epileptic seizures?

Updated: May 30, 2019
  • Author: David Y Ko, MD; Chief Editor: Selim R Benbadis, MD  more...
  • Print

In rodents, recurrent seizures induced by a variety of methods result in a pattern of interneuron loss in the hilar polymorphic region, with striking loss of the neurons that lack the calcium-binding proteins parvalbumin and calbindin. In rat hippocampal sections, these interneurons demonstrate a progressive inability to maintain a hyperpolarized resting membrane potential; eventually, the interneurons die.

In an experiment, researchers used microelectrodes containing the calcium chelator BAPTA and demonstrated reversal of the deterioration in the membrane potential as the calcium chelator was allowed to diffuse in the interneuron. [9] These findings showed the critical role of adequate concentrations of calcium-binding proteins for neuronal survival in settings with sustained rises of intracellular calcium, such as in status epilepticus and other brain insults. This mechanism may contribute to medical intractability in some epilepsy patients.

The vulnerability of interneurons to hypoxia and other insults also correlates to the relative presence of these calcium-binding proteins. The premature loss of interneurons alters inhibitory control over the local neuronal network in favor of net excitation. This effect may explain, for example, why 2 patients who have a similar event (ie, simple febrile convulsion) may have remarkably dissimilar outcomes; that is, one may have completely normal development, and the other may have intractable focal-onset epilepsy after a few years.

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!