Glial regulation of nonsynaptic extracellular glutamate in the substantia nigra.
GLU is the main neurotransmitter in the brain, where it induces a synaptic excitatory action. There is recent evidence for an extracellular nonsynaptic GLU (EnS-GLU) pool in different brain nuclei that, released from glial cells, may act on extrasynaptic GLU receptors of cells located far from the position in which it was released. In the present work, the EnS-GLU pool was studied with microdialysis in the rat substantia nigra (SN). We observed an EnS-GLU pool that increased in a Ca2+-dependent manner during cell depolarization. The selective alteration of with methionine sulfoximide (MSO) and fluorocitrate induced marked modifications in EnS-GLU suggesting that EnS-GLU is dependent on glial cells. Glutamine administration increased GLU, suggesting that neurons are also involved in EnS-GLU modulation. GLU administered in the rostral SN showed a long-distance diffusion to the caudal SN. The ionotropic GLU receptors agonist N-methyl-D-aspartate and kainate and the metabotropic GLU receptors agonist ACPD increased EnS-GLU and decreased extracellular glutamine. Taken together, these data indicate that nigral glia releases GLU, which probably performs a volume transmitter role.
Rodríguez Díaz
Manuel
M
Laboratory of Neurobiology and Experimental Neurology, Department of Physiology, University of La Laguna, La Laguna, Tenerife, Canary Islands, Spain. mrdiaz@ull.es
Alonso
Teofilo Jorge
TJ
Perdomo Diaz
Juan
J
Gonzalez Hernández
Tomás
T
Castro Fuentes
Rafael
R
Sabate
Magdalena
M
Garcia Dopico
Jose
J
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002951:Citrates / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism / Q000494:pharmacology; D006706:Homeostasis / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008717:Methionine Sulfoximine / Q000494:pharmacology; D017551:Microdialysis; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D002951:Citrates; D018690:Excitatory Amino Acid Agonists; D017470:Receptors, Glutamate; D005973:Glutamine; D008717:Methionine Sulfoximine; C007744:fluorocitrate; D018698:Glutamic Acid; D002118:Calcium