Impairment of mitochondrial metabolism differentially affects striatal neuronal subtypes

Electrophysiological and microfluorometric measurements were combined to analyse the responses of rat striatal medium spiny (MS) and large aspiny (LA) interneurons to the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylidrazone (FCCP). FCCP produced a membrane depolarisation coupled to an irreversible increase in intracellular calcium [Ca²⁺]_i in MS. Conversely, LA interneurons hyperpolarised and a moderate [Ca²⁺]_i rise was observed. Cyclosporin A, inhibitor of the mitochondrial membrane transition pore, prevented the FCCP-induced changes in LA interneurons, whereas only a partial reduction was observed in MS cells. The present results indicate that mitochondrial Ca²⁺ released into the cytosol may contribute to the selective vulnerability to metabolic impairment in striatal neuronal subtypes.