Mitochondria modulate Ca2+-dependent glutamate release from rat cortical astrocytes.
Vesicular glutamate release from astrocytes depends on mobilization of free Ca(2+) from the endoplasmic reticulum (ER), and extracellular space to elevate cytosolic Ca(2+) (Ca(2+)(cyt)). Although mitochondria in neurons, and other secretory cells, have been shown to sequester free Ca(2+) and have been implicated in the modulation of Ca(2+)-dependent transmitter release, the role of mitochondria in Ca(2+)-dependent glutamate release from astrocytes is not known. A pharmacological approach was taken to manipulate Ca(2+) accumulation in mitochondria and thereby affect Ca(2+)(cyt) of solitary astrocytes in response to mechanical stimuli. Ca(2+)(cyt) responses and levels of glutamate release were measured optically in parallel experiments using a fluorescent Ca(2+) indicator and an enzyme-linked assay, respectively. It was observed that inhibiting mitochondrial Ca(2+) accumulation is correlated to increased Ca(2+)(cyt) and glutamate release, whereas enhancing mitochondrial Ca(2+) accumulation is correlated to decreased Ca(2+)(cyt) and glutamate release. These observations suggest that, in addition to the activity of ER and plasma membrane ion channels, mitochondria modulate Ca(2+)(cyt) dynamics in astrocytes and play a role in Ca(2+)-dependent glutamate release from astrocytes.
Reyes
Reno C
RC
Department of Neurobiology, Center for Glial Biology in Medicine, Atomic Force Microscopy and Nanotechnology Laboratories, Civitan International Research Center, Evelyn F. McKnight Brain Institute, University of Alabama, Birmingham, Alabama 35294, USA.
Parpura
Vladimir
V
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure*; D002118:Calcium / Q000378:metabolism*; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002998:Clonazepam / Q000031:analogs & derivatives / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology; D010812:Physical Stimulation / Q000379:methods; D011726:Pyridinium Compounds / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017975:Ruthenium Compounds / Q000494:pharmacology; D022142:Secretory Vesicles / Q000187:drug effects; D013401:Sugar Alcohol Dehydrogenases / Q000378:metabolism; D013841:Thiazepines / Q000494:pharmacology; D014793:Visual Cortex / Q000166:cytology*
D004791:Enzyme Inhibitors; D009840:Oligomycins; D011726:Pyridinium Compounds; C112020:Ru 360; D017975:Ruthenium Compounds; D013841:Thiazepines; C052247:4-(4-diethylaminostyryl)-N-methylpyridinium; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D018698:Glutamic Acid; D002998:Clonazepam; C079032:CGP 37157; D016572:Cyclosporine; D013401:Sugar Alcohol Dehydrogenases; C095946:galactitol 2-dehydrogenase; D002118:Calcium