Mitochondria Modulate Ca2+-Dependent Glutamate Release from Rat Cortical Astrocytes

Abstract

Vesicular glutamate release from astrocytes depends on mobilization of free Ca²⁺from the endoplasmic reticulum (ER), and extracellular space to elevate cytosolic Ca²⁺(Ca²⁺_cyt). Although mitochondria in neurons, and other secretory cells, have been shown to sequester free Ca²⁺and have been implicated in the modulation of Ca²⁺-dependent transmitter release, the role of mitochondria in Ca²⁺-dependent glutamate release from astrocytes is not known. A pharmacological approach was taken to manipulate Ca²⁺accumulation in mitochondria and thereby affect Ca²⁺_cytof solitary astrocytes in response to mechanical stimuli. Ca²⁺_cytresponses and levels of glutamate release were measured optically in parallel experiments using a fluorescent Ca²⁺indicator and an enzyme-linked assay, respectively. It was observed that inhibiting mitochondrial Ca²⁺accumulation is correlated to increased Ca²⁺_cytand glutamate release, whereas enhancing mitochondrial Ca²⁺accumulation is correlated to decreased Ca²⁺_cytand glutamate release. These observations suggest that, in addition to the activity of ER and plasma membrane ion channels, mitochondria modulate Ca²⁺_cytdynamics in astrocytes and play a role in Ca²⁺-dependent glutamate release from astrocytes.