Journal
ASN NEURO
Volume 4, Issue 1, Pages 33-45Publisher
SAGE PUBLICATIONS LTD
DOI: 10.1042/AN20110059
Keywords
astrocyte; calcium; calcium signalling; glutamate release; sodium; sodium-calcium exchanger
Categories
Funding
- National Institute of Mental Health [MH 069791]
- National Science Foundation [CBET 0943343]
- NATIONAL INSTITUTE OF MENTAL HEALTH [R01MH069791] Funding Source: NIH RePORTER
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Astroglial excitability operates through increases in Ca-cyt(2+) (cytosolic Ca2+), which can lead to glutamatergic glio-transmission. 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 Ca-cyt(2+) 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).
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