Possible involvement of different connexin43 domains in plasma membrane permeabilization induced by ischemia-reperfusion.
In vitro and in vivo studies support the involvement of connexin 43-based cell-cell channels and hemichannels in cell death propagation induced by ischemia-reperfusion. In this context, open connexin hemichannels in the plasma membrane have been proposed to act as accelerators of cell death. Progress on the mechanisms underlying the cell permeabilization induced by ischemia-reperfusion reveals the involvement of several factors leading to an augmented open probability and increased number of hemichannels on the cell surface. While open probability can be increased by a reduction in extracellular concentration of divalent cations and changes in covalent modifications of connexin 43 (oxidation and phosphorylation), increase in number of hemichannels requires an elevation of the intracellular free Ca(2+) concentration. Reversal of connexin 43 redox changes and membrane permeabilization can be induced by intracellular, but not extracellular, reducing agents, suggesting a cytoplasmic localization of the redox sensor(s). In agreement, hemichannels formed by connexin 45, which lacks cytoplasmic cysteines, or by connexin 43 with its C-terminal domain truncated to remove its cysteines are insensitive to reducing agents. Although further studies are required for a precise localization of the redox sensor of connexin 43 hemichannels, modulation of the redox potential is proposed as a target for the design of pharmacological tools to reduce cell death induced by ischemia-reperfusion in connexin 43-expressing cells.
Retamal
Mauricio A
MA
Departamento de Ciencias Fisiológicas, Pontificia Universidad Católica de Chile, Alameda 340, Santiago, Chile.
Schalper
Kurt A
KA
Shoji
Kenji F
KF
Orellana
Juan A
JA
Bennett
Michael V L
MV
Sáez
Juan C
JC
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D002463:Cell Membrane Permeability; D018031:Connexin 43 / Q000502:physiology*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism*
D018031:Connexin 43; D007473:Ion Channels
J Cell Physiol. 2003 Nov;197(2):205-13
14502560
FASEB J. 2001 Jan;15(1):10-12
11099492
J Biol Chem. 2007 Mar 23;282(12 ):8895-904
17227765
Mol Pharmacol. 2007 Feb;71(2):570-9
17095584
Int J Mol Med. 2002 Dec;10(6):671-6
12429990
J Biol Chem. 2002 Nov 22;277(47):44962-8
12270943
Acta Physiol Scand. 2003 Sep;179(1):23-31
12940935
Biophys J. 2002 Apr;82(4):2016-31
11916859
Pflugers Arch. 2000 Jul;440(3):366-79
10954323
FEBS Lett. 2004 Aug 13;572(1-3):65-8
15304325
J Biol Chem. 2004 Jan 23;279(4):2913-21
14583621
J Biol Chem. 1999 Jan 1;274(1):236-40
9867835
Neuroreport. 1995 Oct 2;6(14):1909-12
8547596
Trends Neurosci. 2003 Nov;26(11):610-7
14585601
Nat Rev Mol Cell Biol. 2005 Feb;6(2):150-66
15688001
Science. 2002 Apr 19;296(5567):503-7
11964472
Methods Find Exp Clin Pharmacol. 1999 Jul-Aug;21(6):387-90
10445229
Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5836-41
8650179
Biochem J. 2006 Jul 1;397(1):1-14
16761954
J Biol Chem. 1999 Feb 26;274(9):5581-7
10026174
Stroke. 2007 Feb;38(2 Suppl):674-6
17261713
Annu Rev Physiol. 1999;61:283-310
10099690
Biophys J. 1995 May;68(5):1796-803
7612821
Lancet. 2007 Jan 27;369(9558):331-41
17258673
J Cell Biol. 1994 Oct;127(2):343-55
7929580
Circ Res. 1992 Feb;70(2):438-44
1310450
FASEB J. 2005 Dec;19(14):2075-7
16204355
J Mol Cell Cardiol. 2000 Oct;32(10):1859-72
11013130
N Engl J Med. 1999 Nov 11;341(20):1543-4
10559458
J Gen Physiol. 1993 Jul;102(1):59-74
7690837
Annu Rev Physiol. 1995;57:311-32
7778871
FEBS Lett. 2006 Jan 9;580(1):239-44
16364313
Neurology. 1999 Jan 15;52(2):280-4
9932944
Cell Tissue Res. 2006 Nov;326(2):239-48
16896946
J Clin Invest. 1991 Jul;88(1):331-5
2056126
Circ Res. 2004 Oct 1;95(7):726-33
15358666
Glia. 1998 Sep;24(1):141-54
9700496
Proc Natl Acad Sci U S A. 2007 Mar 20;104(12):4919-24
17360407
Neuron. 2005 Jun 2;46(5):731-44
15924860
Clin Exp Dermatol. 2003 Jul;28(4):397-409
12823303
J Biol Chem. 2004 Mar 12;279(11):9689-92
14676187
Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13644-9
14597722
Proc Natl Acad Sci U S A. 2006 Jun 20;103(25):9726-31
16772377
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16030-5
14663144
Nat Med. 2006 Aug;12(8):950-4
16862155
Physiology (Bethesda). 2006 Apr;21:103-14
16565476
Trends Neurosci. 1999 Sep;22(9):391-7
10441299
Braz J Med Biol Res. 1998 May;31(5):593-600
9698763
Arch Biochem Biophys. 2006 Jun 1;450(1):78-88
16620764
J Gen Physiol. 1999 May;113(5):721-42
10228184
J Cell Biol. 1991 Nov;115(4):1077-89
1659572
Brain Res Brain Res Rev. 2000 Apr;32(1):250-8
10751675
Stroke. 2001 Oct;32(10):2426-32
11588337
J Gen Physiol. 2004 Nov;124(5):587-603
15504903
J Cell Biol. 2000 Mar 6;148(5):1063-74
10704454
Proc Natl Acad Sci U S A. 2003 Sep 30;100(20):11388-93
13130072
J Cell Biol. 1996 Aug;134(4):1019-30
8769424
J Gen Physiol. 1999 Apr;113(4):507-24
10102933
Am J Physiol Cell Physiol. 2004 Nov;287(5):C1389-95
15475518
J Gen Physiol. 1994 Dec;104(6):1039-55
7535344
J Biol Chem. 2004 May 7;279(19):20058-66
14973142
Glia. 2003 Sep;43(3):265-73
12898705
J Neurosci. 2003 May 1;23(9):3588-96
12736329
EMBO J. 2006 Nov 1;25(21):5071-82
17036048
J Biol Chem. 1998 Apr 10;273(15):9188-96
9535909
Vis Neurosci. 2004 Jul-Aug;21(4):501-11
15579217
J Membr Biol. 2004 Jun 1;199(3):143-54
15457371
Cell. 2007 Feb 9;128(3):547-60
17289573
Eur J Neurosci. 1999 Jun;11(6):1883-90
10336656
Am J Physiol Cell Physiol. 2004 Oct;287(4):C817-33
15355853
J Membr Biol. 2000 Jan 1;173(1):39-46
10612690
Am J Physiol Cell Physiol. 2004 Mar;286(3):C647-54
14602580
J Mol Cell Cardiol. 1997 Aug;29(8):2131-45
9281445
Glia. 2007 Jan 1;55(1):46-56
17009242
Cell Mol Neurobiol. 2004 Oct;24(5):647-65
15485136
Nat Rev Mol Cell Biol. 2003 Apr;4(4):285-94
12671651
Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4475-80
16537412
J Biol Chem. 2006 Jul 28;281(30):21362-8
16720574
J Gen Physiol. 2005 Feb;125(2):127-41
15657297
Neurosci Lett. 2007 Mar 19;415(1):45-8
17222973
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):495-500
11756680
J Neurosci Methods. 2002 Nov 15;121(1):81-92
12393164
Biophys J. 2006 Sep 15;91(6):2142-54
16798801
Biochim Biophys Acta. 2005 Jun 10;1711(2):208-14
15955305
Metab Brain Dis. 2004 Dec;19(3-4):151-67
15554412
Eur J Neurosci. 2000 Jul;12(7):2644-50
10947839
Brain Res Brain Res Rev. 2004 Dec;47(1-3):290-303
15572178
Circ Res. 1981 Jan;48(1):1-16
7438341
J Biol Chem. 2002 Dec 13;277(50):48295-302
12376535
Ann Neurol. 2005 May;57(5):749-54
15852376
J Bone Miner Res. 2001 Aug;16(8):1465-76
11499869
J Neurosci. 1998 Apr 1;18(7):2520-37
9502812
Mol Biol Cell. 2005 Jul;16(7):3100-6
15843434
Dev Genet. 1999;24(1-2):123-36
10079516
Cell Calcium. 2003 Jan;33(1):37-48
12526886
J Comp Neurol. 2003 Nov 24;466(4):468-77
14566943
FASEB J. 2006 Nov;20(13):2329-38
17077310
Am J Pathol. 2004 Jun;164(6):2067-75
15161641
Cell. 2004 Sep 17;118(6):687-98
15369669
J Cereb Blood Flow Metab. 1997 Nov;17(11):1170-81
9390649
Stroke. 1993 Nov;24(11):1709-16
7694393
J Neurosci Res. 1993 Jun 15;35(3):237-45
7688816
Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1208-18
15790881
Cell Mol Life Sci. 1999 Jul;55(8-9):1036-42
10442087
Diabetes. 2006 Feb;55(2):349-55
16443767
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3980-4
11891346
Curr Opin Cell Biol. 2004 Oct;16(5):507-12
15363800
J Clin Invest. 2005 Mar;115(3):500-8
15765131
Cell. 1994 Sep 23;78(6):931-6
7923362
Mol Biol Cell. 2007 Jan;18(1):34-46
17079735
EMBO J. 2006 Jan 11;25(1):34-44
16341088
Science. 2006 May 12;312(5775):924-7
16690868
Biochim Biophys Acta. 2005 Jun 10;1711(2):215-24
15955306
J Gen Physiol. 2002 Feb;119(2):147-64
11815665
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9840-5
12097649
Cell. 1993 Sep 24;74(6):1065-77
7691412
Cell Growth Differ. 1998 Jan;9(1):13-21
9438384
Physiol Rev. 1999 Oct;79(4):1431-568
10508238
J Membr Biol. 2003 Dec 1;196(3):173-84
14724743
Pflugers Arch. 1999 Feb;437(3):345-53
9914390
Invest Ophthalmol Vis Sci. 1994 Sep;35(10):3747-58
8088962
Eur J Neurosci. 2005 Apr;21(7):1859-68
15869481
Biophys J. 1996 Aug;71(2):742-8
8842212
J Exp Biol. 2005 Apr;208(Pt 8):1415-9
15802665
J Biol Chem. 2004 Aug 27;279(35):36993-7003
15213236
Proc Natl Acad Sci U S A. 2006 May 16;103(20):7655-9
16682648
J Biol Chem. 2002 Mar 22;277(12):10482-8
11790776
Pflugers Arch. 1998 Jul;436(4):627-9
9683738
Biorheology. 2003;40(1-3):119-21
12454395
AAPS J. 2006 May 05;8(2):E314-21
16796382
Brain Res. 1990 Feb 5;508(2):313-9
2155040
Int J Biochem Cell Biol. 2004 Jul;36(7):1171-86
15109565
Am J Physiol Cell Physiol. 2004 Dec;287(6):C1596-604
15282192
J Membr Biol. 2002 Jan 15;185(2):93-102
11891568
J Physiol. 1992 Jan;445:201-30
1380084
J Neurochem. 2005 Mar;92(5):1033-43
15715654
Biophys J. 2005 Mar;88(3):1725-39
15596513
J Mol Cell Cardiol. 2001 Dec;33(12):2145-55
11735261
Am J Physiol Cell Physiol. 2007 Jul;293(1):C337-45
17428836
Toxicol Sci. 2006 Jan;89(1):265-70
16237196
J Neurotrauma. 1995 Oct;12(5):943-56
8594224
Mol Vis. 2001 Nov 16;7:247-52
11715013
J Cell Physiol. 2006 Jan;206(1):95-102
15965959
J Neurol Sci. 1995 Jan;128(1):22-7
7536815
Mol Biol Cell. 2005 Nov;16(11):5247-57
16135529
Am J Physiol Lung Cell Mol Physiol. 2004 Sep;287(3):L497-502
15145787
Postgrad Med J. 2002 Nov;78(925):641-5
12496316
Biophys J. 2003 Jan;84(1):277-86
12524281
Proc Natl Acad Sci U S A. 2007 May 15;104(20):8322-7
17494739
Int Rev Cytol. 2003;224:29-55
12722948
Circ Res. 2000 Oct 13;87(8):656-62
11029400
Laryngoscope. 2006 Dec;116(12 ):2205-10
17146396
Hum Mol Genet. 2004 Aug 15;13(16):1703-14
15213106
Cardiovasc Res. 2005 Aug 1;67(2):234-44
15919068