A.G. and D.S. contributed equally to this work.
Stromal-cell-derived factor 1α /CXCL12 modulates high-threshold calcium currents in rat substantia nigra
Article first published online: 30 JUL 2008
© The Authors (2008). Journal Compilation © Federation of European Neuroscience Societies and Blackwell Publishing Ltd
European Journal of Neuroscience
Volume 28, Issue 5, pages 862–870, September 2008
How to Cite
Guyon, A., Skrzydelski, D., Rovère, C., Apartis, E., Rostène, W., Kitabgi, P., Mélik Parsadaniantz, S. and Nahon, J. L. (2008), Stromal-cell-derived factor 1α /CXCL12 modulates high-threshold calcium currents in rat substantia nigra. European Journal of Neuroscience, 28: 862–870. doi: 10.1111/j.1460-9568.2008.06367.x
- Issue published online: 26 AUG 2008
- Article first published online: 30 JUL 2008
- Received 12 February 2008, revised 6 June 2008, accepted 11 June 2008
- dopaminergic neuron;
- HVA Ca currents;
- stromal-cell-derived factor 1α
Dopaminergic neurons of the substantia nigra constitutively express the CXCR4 receptor for the chemokine stromal-cell-derived factor 1α (CXCL12) but, to date, no direct effect of CXCR4 activation by CXCL12 on membrane conductance of dopaminergic neurons has been demonstrated. We tested the effects of CXCL12 on whole-cell currents of dopaminergic neurons recorded in patch clamp in substantia nigra slices and showed that CXCL12 (0.01–10 nm) increased the amplitude of total high-voltage-activated (HVA) Ca currents through CXCR4 activation. This effect was reversibly reduced by ϖ-conotoxin-GVIA, suggesting that CXCL12 acted on N-type Ca currents, known to be involved in dopamine (DA) release. We therefore investigated the effects of CXCL12 on DA release from cultured dopaminergic neurons from the rat mesencephalon. In basal conditions, CXCL12 alone had no effect on DA release. When neurons were depolarized with KCl (20 mm), and thus when HVA Ca currents were activated, low CXCL12 concentrations (1–50 nm) increased DA release via CXCR4 stimulation. These data strongly suggest that the chemokine CXCL12 can act directly as a neuromodulator of dopaminergic neuronal electrical activity through the modulation of HVA currents.