| 11245674 |
Rego AC, Ward MW, Nicholls DG: Mitochondria control ampa/kainate receptor-induced cytoplasmic calcium deregulation in rat cerebellar granule cells. J Neurosci. 2001 Mar 15;21(6):1893-901.
Although mitochondria mediate the delayed failure of cytoplasmic Ca (2+) homeostasis [delayed Ca (2+) deregulation (DCD)] in rat cerebellar granule cells resulting from chronic activation of NMDA receptors, their role in AMPA/KA-induced DCD remains to be established. The mitochondrial ATP synthase inhibitor oligomycin protected cells against KA- but not NMDA-evoked DCD. In contrast to NMDA-evoked DCD, no additional protection was afforded by the further addition of rotenone. The effects of KA on cytoplasmic Ca (2+) homeostasis, including the protection afforded by oligomycin, could be reproduced by veratridine. KA exposure induced a partial mitochondrial depolarization that was enhanced by oligomycin, indicating ATP synthase reversal. The nonglycolytic substrates pyruvate and lactate were unable to maintain Ca (2+) homeostasis in the presence of KA. In contrast to NMDA, KA exposure did not cause mitochondrial Ca (2+) loading. The data indicate that Na (+) entry via noninactivating AMPA/KA receptors or voltage-activated Na (+) channels compromises mitochondrial function sufficiently to cause ATP synthase reversal. Oligomycin may protect by preventing the consequent mitochondrial drain of cytoplasmic ATP. |
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