Plasmalemmal Na+/Ca2+ exchanger modulates Ca2+-dependent exocytotic release of glutamate from rat cortical astrocytes

Academic Article

Abstract

  • Astroglial excitability operates through increases in Ca (cytosolic Ca ), which can lead to glutamatergic gliotransmission. In parallel fluctuations in astrocytic Na (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 Ca -ATPase), NCX (plasma membrane Na /Ca exchanger) and NKA (Na /K -ATPase) in complex and coordinated regulation of Ca and Na in astrocytes at rest and upon mechanical stimulation. Our data support the notion that NKA and PMCA are the major Na and Ca extruders in resting astrocytes. Surprisingly, the blockade of NKA or PMCA appeared less important during times of Ca and Na cytosolic loads caused by mechanical stimulation. Unexpectedly, NCX in reverse mode appeared as a major contributor to overall Ca and Na homoeostasis in astrocytes both at rest and when these glial cells were mechanically stimulated. In addition, NCX facilitated mechanically induced Ca -dependent exocytotic release of glutamate from astrocytes. These findings help better understanding of astrocyte-neuron bidirectional signaling at the tripartite synapse and/or microvasculature. We propose that NCX operating in reverse mode could be involved in fast and spatially localized Ca -dependent gliotransmission, that would operate in parallel to a slower and more widely distributed gliotransmission pathway that requires metabotropically controlled Ca release from the ER (endoplasmic reticulum). © 2012 The Author(s). 2+ 2+ + + 2+ + 2+ + + 2+ + + 2+ 2+ + 2+ + 2+ 2+ 2+ cyt cyt cyt cyt
  • Published In

  • ASN Neuro  Journal
  • Digital Object Identifier (doi)

    Author List

  • Reyes RC; Verkhratsky A; Parpura V
  • Start Page

  • 33
  • End Page

  • 45
  • Volume

  • 4