title: Mitochondrial Ca2+ uptake and release influence metabotropic and ionotropic cytosolic Ca2+ responses in rat oligodendrocyte progenitors.
abstract: 1. Many physiologically important activities of oligodendrocyte progenitor cells (O-2A cells), including proliferation, migration and differentiation, are regulated by cytosolic Ca2+ signals. However, little is known concerning the mechanisms of Ca2+ signalling in this cell type. We have studied the interactions between Ca2+ entry, Ca2+ release from endoplasmic reticulum and Ca2+ regulation by mitochondria in influencing cytosolic Ca2+ responses in O-2A cells. 2. Methacholine (MCh; 100 microM) activated Ca2+ waves that propagated from several initiation sites along O-2A processes. 3. During a Ca2+ wave evoked by MCh, mitochondrial membrane potential was often either depolarized (21 % of mitochondria) or hyperpolarized (20 % of mitochondria), as measured by changes in the fluorescence of 5,5',6,6'-tetrachloro-1,1',3, 3'-tetraethylbenzimidazole carbocyanine iodide (JC-1). 4. Stimulation with kainate (100 microM) evoked a slowly rising, sustained cytosolic Ca2+ elevation in O-2A cells. This also, in some cases, resulted in either a depolarization (15 % of mitochondria) or hyperpolarization (12 % of mitochondria) of mitochondrial membrane potential. 5. Simultaneous measurement of cytosolic (fluo-3 AM) and mitochondrial (rhod-2 AM) Ca2+ responses revealed that Ca2+ elevations in the cytosol evoked by either MCh or kainate were translated into long-lasting Ca2+ elevations in subpopulations of mitochondria. In some mitochondria, Ca2+ signals appeared to activate Ca2+ release into the cytosol. 6. Inhibition of the mitochondrial Na+-Ca2+ exchanger by CGP-37157 (25 microM) decreased kainate Ca2+ response amplitude and increased the rate of return of the response to basal Ca2+ levels. 7. Thus, both ionotropic and metabotropic stimulation evoke changes in mitochondrial membrane potential and Ca2+ levels in O-2A cells. Ca2+ uptake into some mitochondria is activated by Ca2+ entry into cells or release from stores. Mitochondrial Ca2+ release appears to play a key role in shaping kainate-evoked Ca2+ responses.
authors.affiliation: Laboratory of Cellular and Molecular Neurophysiology, National Institute of Child Health and Human Development, NIH, Bethesda, MD 20892-4495, USA.
authors.forename: P B
authors.initials: PB
authors.lastname: Simpson
authors.forename: J T
authors.initials: JT
authors.lastname: Russell
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004558:Electric Stimulation; D018871:Endoplasmic Reticulum, Smooth / Q000187:drug effects / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016210:Methacholine Chloride / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018721:Muscarinic Agonists / Q000494:pharmacology; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D018690:Excitatory Amino Acid Agonists; D018721:Muscarinic Agonists; D019831:Sodium-Calcium Exchanger; D016210:Methacholine Chloride; D007608:Kainic Acid; D002118:Calcium