Dopamine-containing Neurons are Silenced by Energy Deprivation: A Defensive Response or Beginning of Cell Death?

Metabolic stress associated to mitochondrial dysfunction has been put forward as an important factor causing degeneration of mesencephalic dopamine-containing neurons in Parkinson's disease (PD). Here we overview how these neurons react to acute hypoxia or hypoglycemia, that are conditions of energy deprivation causing a reduced production of ATP by mitochondria. These neurons, which show a tonic firing discharge under normal condition, undergo into membrane hyperpolarization during hypoxia or hypoglycemia that silence their spontaneous activity. We outline the cellular mechanisms causing membrane hyperpolarization and the accompanied disturbances of intracellular calcium and sodium homeostasis. A better understanding of the changes occurring during transient energy deprivation might contribute to understand the physiopathology of these neurons that derives from mitochondrial dysfunction.