title: Plasmalemmal Na+/Ca2+ exchanger modulates Ca2+-dependent exocytotic release of glutamate from rat cortical astrocytes.
abstract: Astroglial excitability operates through increases in Ca2+cyt (cytosolic Ca2+), which can lead to glutamatergic gliotransmission. In parallel fluctuations in astrocytic Na+cyt (cytosolic Na+) control metabolic neuronal-glial signalling, most notably through stimulation of lactate production, which on release from astrocytes can be taken up and utilized by nearby neurons, a process referred to as lactate shuttle. Both gliotransmission and lactate shuttle play a role in modulation of synaptic transmission and plasticity. Consequently, we studied the role of the PMCA (plasma membrane Ca2+-ATPase), NCX (plasma membrane Na+/Ca2+ exchanger) and NKA (Na+/K+-ATPase) in complex and coordinated regulation of Ca2+cyt and Na+cyt in astrocytes at rest and upon mechanical stimulation. Our data support the notion that NKA and PMCA are the major Na+ and Ca2+ extruders in resting astrocytes. Surprisingly, the blockade of NKA or PMCA appeared less important during times of Ca2+ and Na+ cytosolic loads caused by mechanical stimulation. Unexpectedly, NCX in reverse mode appeared as a major contributor to overall Ca2+ and Na+ homoeostasis in astrocytes both at rest and when these glial cells were mechanically stimulated. In addition, NCX facilitated mechanically induced Ca2+-dependent exocytotic release of glutamate from astrocytes. These findings help better understanding of astrocyte-neuron bidirectional signalling at the tripartite synapse and/or microvasculature. We propose that NCX operating in reverse mode could be involved in fast and spatially localized Ca2+-dependent gliotransmission, that would operate in parallel to a slower and more widely distributed gliotransmission pathway that requires metabotropically controlled Ca2+ release from the ER (endoplasmic reticulum).
authors.affiliation: 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, AL 35294, USA.
authors.forename: Reno C
authors.initials: RC
authors.lastname: Reyes
authors.forename: Alexei
authors.initials: A
authors.lastname: Verkhratsky
authors.forename: Vladimir
authors.initials: V
authors.lastname: Parpura
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D018920:Coculture Techniques; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D053499:Plasma Membrane Calcium-Transporting ATPases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D012964:Sodium; D053499:Plasma Membrane Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium