PMID- 19166859
OWN - NLM
STAT- MEDLINE
DCOM- 20090506
LR  - 20231213
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 46
IP  - 4
DP  - 2009 Apr
TI  - Functional differences between human Cx37 polymorphic hemichannels.
PG  - 499-507
LID - 10.1016/j.yjmcc.2008.12.018 [doi]
AB  - A polymorphism in the human Cx37 gene (C1019T), resulting in a non-conservative 
      amino acid change in the regulatory C-terminus of the Cx37 protein (P319S), has 
      been proposed as a prognostic marker for atherosclerosis. We have recently 
      demonstrated that Cx37 hemichannels control the initiation of atherosclerotic 
      plaque development by regulating ATP-dependent monocyte adhesion in 
      atherosclerosis-susceptible apolipoprotein E-deficient mice. In this study, we 
      have measured the electrical properties of Cx37 hemichannels (HCs) and gap 
      junction channels (GJCs) with voltage-clamp methods. To this end, we have 
      transfected hCx37-P319, hCx37-S319 or empty pIRES-eGFP vector cDNA into 
      communication-deficient HeLa cells. In clones expressing similar levels of Cx37, 
      exposure of single cells to low-Ca(2+) solution induced a voltage-sensitive HC 
      current. The analysis yielded a bell-shaped function g(hc)=f(V(m)) (g(hc): 
      normalized conductance at steady state; V(m): membrane potential) with a maximum 
      around V(m)=-30 mV. The peak g(hc) of Cx37-P319 was 3-fold larger than that of 
      Cx37-S319 HCs. Experiments on cell pairs revealed that Cx37-P319 GJCs exhibited a 
      1.5-fold larger unitary conductance than Cx37-S319 GJCs. Hence, the larger peak 
      g(hc) of the former may reflect a larger conductance of their HCs. Using the same 
      clones, we found that Cx37-P319 cells released more ATP and were less adhesive 
      than Cx37-S319 cells. The reduction in adhesiveness of Cx37-expressing cells was 
      prevented by extracellular apyrase. We conclude that the differences in 
      biophysical properties between polymorphic HCs may be responsible for inequality 
      in ATP release between Cx37-P319 and Cx37-S319 cells, which results in 
      differential cell adhesion.
FAU - Derouette, Jean-Paul
AU  - Derouette JP
AD  - Department of Internal Medicine, Division of Cardiology, Faculty of Medicine, 
      University of Geneva, Geneva, Switzerland.
FAU - Desplantez, Thomas
AU  - Desplantez T
FAU - Wong, Cindy W
AU  - Wong CW
FAU - Roth, Isabelle
AU  - Roth I
FAU - Kwak, Brenda R
AU  - Kwak BR
FAU - Weingart, Robert
AU  - Weingart R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090107
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Connexins)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Cell Adhesion
MH  - Connexins/*genetics/*metabolism
MH  - Electrophysiological Phenomena
MH  - Gap Junctions/*metabolism
MH  - HeLa Cells
MH  - Humans
MH  - *Polymorphism, Genetic
MH  - Transfection
MH  - Gap Junction alpha-4 Protein
EDAT- 2009/01/27 09:00
MHDA- 2009/05/07 09:00
CRDT- 2009/01/27 09:00
PHST- 2008/04/18 00:00 [received]
PHST- 2008/12/02 00:00 [revised]
PHST- 2008/12/21 00:00 [accepted]
PHST- 2009/01/27 09:00 [entrez]
PHST- 2009/01/27 09:00 [pubmed]
PHST- 2009/05/07 09:00 [medline]
AID - S0022-2828(08)01474-0 [pii]
AID - 10.1016/j.yjmcc.2008.12.018 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2009 Apr;46(4):499-507. doi: 10.1016/j.yjmcc.2008.12.018. 
      Epub 2009 Jan 7.