PMID- 22473778
OWN - NLM
STAT- MEDLINE
DCOM- 20130607
LR  - 20211021
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 590
IP  - 13
DP  - 2012 Jul 1
TI  - The chemokine CXCL12 and the HIV-1 envelope protein gp120 regulate spontaneous 
      activity of Cajal-Retzius cells in opposite directions.
PG  - 3185-202
LID - 10.1113/jphysiol.2011.224873 [doi]
AB  - 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.
FAU - Marchionni, Ivan
AU  - Marchionni I
AD  - Northwestern University, Department of Physiology, Feinberg School of Medicine, 
      303 E Chicago Ave, Tarry Blg Rm 5-707, Chicago, IL 60611, USA.
FAU - Beaumont, Michael
AU  - Beaumont M
FAU - Maccaferri, Gianmaria
AU  - Maccaferri G
LA  - eng
GR  - R01 NS064135/NS/NINDS NIH HHS/United States
GR  - NS064135/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120402
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (CXCR4 protein, mouse)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (Chloride Channels)
RN  - 0 (Cxcl12 protein, mouse)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Potassium Channels, Calcium-Activated)
RN  - 0 (Receptors, CXCR4)
RN  - 0 (gp120 protein, Human immunodeficiency virus 1)
RN  - SY7Q814VUP (Calcium)
SB  - IM
CIN - J Physiol. 2012 Jul 1;590(13):2949-50. PMID: 22753620
MH  - Animals
MH  - Calcium/physiology
MH  - Cell Line
MH  - Chemokine CXCL12/*physiology
MH  - Chloride Channels/physiology
MH  - HIV Envelope Protein gp120/*physiology
MH  - Hippocampus/physiology
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Potassium Channels, Calcium-Activated/physiology
MH  - Receptors, CXCR4/*physiology
PMC - PMC3406399
EDAT- 2012/04/05 06:00
MHDA- 2013/06/08 06:00
PMCR- 2013/07/01
CRDT- 2012/04/05 06:00
PHST- 2012/04/05 06:00 [entrez]
PHST- 2012/04/05 06:00 [pubmed]
PHST- 2013/06/08 06:00 [medline]
PHST- 2013/07/01 00:00 [pmc-release]
AID - jphysiol.2011.224873 [pii]
AID - 10.1113/jphysiol.2011.224873 [doi]
PST - ppublish
SO  - J Physiol. 2012 Jul 1;590(13):3185-202. doi: 10.1113/jphysiol.2011.224873. Epub 
      2012 Apr 2.