Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling.
Neurotransmitter release generally is considered to occur at active zones of synapses, and ectopic release of neurotransmitters has been demonstrated in a few instances. However, the mechanism of ectopic neurotransmitter release is poorly understood. We took advantage of the intimate morphological and functional proximity of olfactory receptor axons and specialized glial cells, olfactory ensheathing cells (OECs), to study ectopic neurotransmitter release. Axonal stimulation evoked purinergic and glutamatergic Ca(2+) responses in OECs, indicating ATP and glutamate release. In axons expressing synapto-pHluorin, stimulation evoked an increase in synapto-pHluorin fluorescence, indicative of vesicle fusion. Transmitter release was dependent on Ca(2+) and could be inhibited by bafilomycin A1 and botulinum toxin A. Ca(2+) transients in OECs evoked by ATP, axonal stimulation, and laser photolysis of NP-EGTA resulted in constriction of adjacent blood vessels. Our results indicate that ATP and glutamate are released ectopically by vesicles along axons and mediate neurovascular coupling via glial Ca(2+) signaling.
Thyssen
Anne
A
Abteilung für Allgemeine Zoologie, Technische Universität Kaiserslautern, 67653 Kaiserslautern, Germany.
Hirnet
Daniela
D
Wolburg
Hartwig
H
Schmalzing
Günther
G
Deitmer
Joachim W
JW
Lohr
Christian
C
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D004110:Diltiazem / Q000494:pharmacology; D004558:Electric Stimulation; D018698:Glutamic Acid / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D009457:Neuroglia / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009830:Olfactory Bulb / Q000098:blood supply / Q000166:cytology / Q000502:physiology; D018034:Olfactory Receptor Neurons / Q000098:blood supply* / Q000502:physiology*; D011984:Sensory Receptor Cells / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology; D014661:Vasoconstriction / Q000502:physiology
D015220:Calcium Channels; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D004110:Diltiazem