| First Author | Marchionni I | Year | 2012 |
| Journal | J Physiol | Volume | 590 |
| Issue | 13 | Pages | 3185-202 |
| PubMed ID | 22473778 | Mgi Jnum | J:250727 |
| Mgi Id | MGI:6099180 | Doi | 10.1113/jphysiol.2011.224873 |
| Citation | Marchionni I, et al. (2012) The chemokine CXCL12 and the HIV-1 envelope protein gp120 regulate spontaneous activity of Cajal-Retzius cells in opposite directions. J Physiol 590(13):3185-202 |
| abstractText | Activation of the CXC chemokine receptor 4 (CXCR4) in Cajal-Retzius cells by CXC chemokine ligand 12 (CXCL12) is important for controlling their excitability. CXCR4 is also a co-receptor for the glycoprotein 120 (gp120) of the envelope of the human immunodeficiency virus type 1 (HIV-1), and binding of gp120 to CXCR4 may produce pathological effects. In order to study CXCR4-dependent modulation of membrane excitability, we recorded in cell-attached configuration spontaneous action currents from hippocampal stratum lacunosum-moleculare Cajal-Retzius cells of the CXCR4-EGFP mouse. CXCL12 (50 nM) powerfully inhibited firing independently of synaptic transmission, suggesting that CXCR4 regulates an intrinsic conductance. This effect was prevented by conditioning slices with BAPTA-AM (200 muM), and by blockers of the BK calcium-dependent potassium channels (TEA (1 mM), paxilline (10 muM) and iberiotoxin (100 nM)). In contrast, exposure to gp120 (pico- to nanomolar range, alone or in combination with soluble cluster of differentiation 4 (CD4)), enhanced spontaneous firing frequency. This effect was prevented by the CXCR4 antagonist AMD3100 (1 muM) and was absent in EGFP-negative stratum lacunosum-moleculare interneurons. Increased excitability was prevented by treating slices with BAPTA-AM or bumetanide, suggesting that gp120 activates a mechanism that is both calcium- and chloride-dependent. In conclusion, our results demonstrate that CXCL12 and gp120 modulate the excitability of Cajal-Retzius cells in opposite directions. We propose that CXCL12 and gp120 either generate calcium responses of different strength or activate distinct pools of intracellular calcium, leading to agonist-specific responses, mediated by BK channels in the case of CXCL12, and by a chloride-dependent mechanism in the case of gp120. |
