Mitochondrial Control of Acute Glutamate Excitotoxicity in Cultured Cerebellar Granule Cells

摘要: Mitochondria within cultured rat cerebellar granule cells have a complex influence on cytoplasmic free Ca2+([Ca2+]c) responses to glutamate. A decreased initial [Ca2+]celevation in whose mitochondria are depolarized by inhibition of the ATP synthase and respiratory chain (conditions which avoid depletion) was attributed enhanced Ca2+ extrusion from cell rather than inhibited entry via NMDA receptor. Even presence elevated extracellular Ca2+, when [Ca2+]cresponses were restored control values, such showed resistance acute excitotoxicity, defined as delayed deregulation (DCD) during glutamate exposure. DCD function duration mitochondrial polarization total period Once initiated, could not be reversed receptor inhibition. In absence inhibition, inhibitors produced an immediate Ca2+deregulation (ICD), ascribed deficit. contrast DCD, ICD subsequent with or without additional blockade. failure yielding metabolic pathway. It is concluded that can glutamate-exposed plasma membrane three ways: competing efflux pathways for restricting supply, inducing extrusion. Inhibitors permeability transition only marginally onset DCD.