Calcium, neuronal hyperexcitability and ischemic injury.
Due to tight regulatory controls, a 10,000-fold concentration gradient exists between intracellular and extracellular free Ca2+ concentrations. With appropriate stimulus Ca2+ will rapidly flow into neurons through various types of membrane channels including voltage-dependent and receptor-operated channels. Intracellular Ca2+ concentrations are then quickly restored primarily through Ca2+-ATPase, Na+/Ca2+ exchange, and endoplasmic reticulum sequestration. It is well-known that Ca2+ is essential for neurotransmitter release. More recent investigations indicate that Ca2+ influx is essential for neuronal excitability independent from synaptic function. In fact, abnormal Ca2+ metabolism may play a dominant role in both the initiation and propagation of seizure discharge. Accordingly, Ca2+ channel blockers may represent a new therapeutic modality to treat epilepsy. Analyzed in this article are the major mechanisms by which neurons control Ca2+ fluxes and the evidence supporting the role of Ca2+ in seizure phenomena. Thereafter, an integrative theory for the role of calcium in neuronal hyperexcitability and ischemic cell death is constructed.
Meyer
F B
FB
Department of Neurosurgery, Mayo Clinic, Rochester 55905.
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology; D004827:Epilepsy / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans
D015220:Calcium Channels; D002118:Calcium