SDF-1alpha-mediated modulation of synaptic transmission in rat cerebellum.
The functional expression of the seven-transmembrane domain G protein-coupled chemokine receptor CXCR-4/fusin in rat nerve cell was demonstrated by staining with a polyclonal anti-CXCR-4 Ab, and by evaluating the calcium responses to the physiological agonist stromal-derived cell factor-1alpha (SDF-1alpha) in both cerebellar granule cells in culture and Purkinje neurons (PNs) in cerebellar slices. Cerebellar glial, granule and Purkinje cells showed a pronounced staining for CXCR-4. Furthermore, cultured granule cells exhibited Ca2+ transients elicited by the application of SDF-1alpha, both in cell bodies and in neuronal processes. Whole-cell patch-clamped PNs in cerebellar slices responded to SDF-1alpha application by a slow inward current followed by an increase of both intracellular Ca2+ level and spontaneous synaptic activity. In particular, the SDF-1alpha-induced slow inward current was considerably reduced by ionotropic glutamate receptor blockers, but developed fully in a medium in which synaptic transmission was inhibited, indicating that this current might be, at least in part, mediated by extrasynaptic glutamate, possibly released from the surrounding glial and/or nerve cells. Taken together, these findings indicate a functional involvement of CXCR-4 in the modulation of synaptic transmission, adding another member to the repertoire of the chemokine receptors exerting a neuromodulatory role in the cerebellum.
Limatola
C
C
Dipartimento Medicina Sperimentale e Patologia, Università di Roma 'La Sapienza', Roma, Italy. limatola@axrma.uniroma1.it
Giovannelli
A
A
Maggi
L
L
Ragozzino
D
D
Castellani
L
L
Ciotti
M T
MT
Vacca
F
F
Mercanti
D
D
Santoni
A
A
Eusebi
F
F
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000906:Antibodies; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D004594:Electrophysiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D017628:Microglia / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D018613:Microscopy, Confocal; D015213:Neuroimmunomodulation / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D011689:Purkinje Cells / Q000737:chemistry / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D019718:Receptors, CXCR4 / Q000032:analysis / Q000276:immunology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D000906:Antibodies; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D018691:Excitatory Amino Acid Antagonists; D019718:Receptors, CXCR4; D013779:Tetrodotoxin; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002118:Calcium