Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy.
Glial cells actively participate in synaptic transmission. They clear molecules from the synaptic cleft, receive signals from neurons and, in turn, release molecules that can modulate signaling between neuronal elements. Whether glial-derived transmitters can contribute to enduring changes in postsynaptic efficacy, however, remains to be established. In rat hypothalamic paraventricular nucleus, we demonstrate an increase in the amplitude of miniature excitatory postsynaptic currents in response to norepinephrine that requires the release of ATP from glial cells. The increase in quantal efficacy, which likely results from an insertion of AMPA receptors, is secondary to the activation of P2X(7) receptors, an increase in postsynaptic calcium and the activation of phosphatidylinositol 3-kinase. The gliotransmitter ATP, therefore, contributes directly to the regulation of postsynaptic efficacy at glutamatergic synapses in the CNS.
Gordon
Grant R J
GR
Hotchkiss Brain Institute and the Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
Baimoukhametova
Dinara V
DV
Hewitt
Sarah A
SA
Rajapaksha
W R A Kosala J S
WR
Fisher
Thomas E
TE
Bains
Jaideep S
JS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018048:Receptors, Purinergic P2 / Q000378:metabolism; D058486:Receptors, Purinergic P2X7; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution
D015415:Biomarkers; C546470:P2rx7 protein, rat; D018091:Receptors, AMPA; D018340:Receptors, Adrenergic, alpha-1; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate; D019869:Phosphatidylinositol 3-Kinases; D002118:Calcium; D009638:Norepinephrine