Role of connexins and pannexins in cardiovascular physiology

Cellular and Molecular Life Sciences

Volumn 72, Issue 15, 2015, Pages 2779-2792

  Meens, Merlijn J ^a   Kwak, Brenda R ^a   Duffy, Heather S ^b  

^a UNIVERSITY OF GENEVA   (Switzerland)

^b Creative Innovation Consulting   (United States)

Author keywords

Cardiovascular; Connexins; Gap junction channel; Hemichannel; Pannexins; Physiology

Indexed keywords

CELL PROTEIN; CONNEXIN 37; GAP JUNCTION PROTEIN; NITRIC OXIDE SYNTHASE; PANNEXIN; UNCLASSIFIED DRUG; ION CHANNEL;

ARTERIOLE; ARTICLE; CARDIOVASCULAR FUNCTION; COMPLEX FORMATION; ENZYME REGULATION; GAP JUNCTION; HEART CONDUCTION; HEART MUSCLE CELL; HUMAN; INTRACELLULAR SIGNALING; NONHUMAN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; VASCULAR RESISTANCE; ANIMAL; CARDIOVASCULAR SYSTEM; METABOLISM; PHYSIOLOGY;

ANIMALS; CARDIOVASCULAR PHYSIOLOGICAL PHENOMENA; CARDIOVASCULAR SYSTEM; CONNEXINS; GAP JUNCTIONS; HUMANS; ION CHANNELS;

EID: 84937728214     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-015-1959-2     Document Type: Article

References (164)

1. Saez JC, Leybaert L (2014) Hunting for connexin hemichannels. FEBS Lett 588(8):1205-1211. doi: 10.1016/j.febslet.2014.03.004
2. Penuela S, Bhalla R, Gong XQ, Cowan KN, Celetti SJ, Cowan BJ, Bai D, Shao Q, Laird DW (2007) Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J Cell Sci 120(Pt 21):3772-3783. doi: 10.1242/jcs.009514
3. Riteau N, Baron L, Villeret B, Guillou N, Savigny F, Ryffel B, Rassendren F, Le Bert M, Gombault A, Couillin I (2012) ATP release and purinergic signaling: a common pathway for particle-mediated inflammasome activation. Cell Death Dis 3:e403. doi: 10.1038/cddis.2012.144
4. Sosinsky GE, Boassa D, Dermietzel R, Duffy HS, Laird DW, MacVicar B, Naus CC, Penuela S, Scemes E, Spray DC, Thompson RJ, Zhao HB, Dahl G (2011) Pannexin channels are not gap junction hemichannels. Channels (Austin) 5(3):193-197. doi: 10.4161/chan.5.3.15765
5. Velasquez S, Eugenin EA (2014) Role of Pannexin-1 hemichannels and purinergic receptors in the pathogenesis of human diseases. Front Physiol 5:96. doi: 10.3389/fphys.2014.00096
6. Adamson SE, Leitinger N (2014) The role of pannexin1 in the induction and resolution of inflammation. FEBS Lett 588(8):1416-1422. doi: 10.1016/j.febslet.2014.03.009
7. Jansen JA, van Veen TA, de Bakker JM, van Rijen HV (2010) Cardiac connexins and impulse propagation. J Mol Cell Cardiol 48(1):76-82. doi: 10.1016/j.yjmcc.2009.08.018
8. Laird DW (2010) The gap junction proteome and its relationship to disease. Trends Cell Biol 20(2):92-101. doi: 10.1016/j.tcb.2009.11.001
9. Duffy HS, Fort AG, Spray DC (2006) Cardiac connexins: genes to nexus. Adv Cardiol 42:1-17. doi: 10.1159/000092550
10. Kreuzberg MM, Liebermann M, Segschneider S, Dobrowolski R, Dobrzynski H, Kaba R, Rowlinson G, Dupont E, Severs NJ, Willecke K (2009) Human connexin31.9, unlike its orthologous protein connexin30.2 in the mouse, is not detectable in the human cardiac conduction system. J Mol Cell Cardiol 46(4):553-559. doi: 10.1016/j.yjmcc.2008.12.007
11. Davis LM, Kanter HL, Beyer EC, Saffitz JE (1994) Distinct gap junction protein phenotypes in cardiac tissues with disparate conduction properties. J Am Coll Cardiol 24(4):1124-1132. doi: 10.1016/0735-1097(94)90879-6
12. Davis LM, Rodefeld ME, Green K, Beyer EC, Saffitz JE (1995) Gap junction protein phenotypes of the human heart and conduction system. J Cardiovasc Electrophysiol 6(10 Pt 1):813-822
13. Beyer EC, Davis LM, Saffitz JE, Veenstra RD (1995) Cardiac intercellular communication: consequences of connexin distribution and diversity. Braz J Med Biol Res 28(4):415-425
14. Saffitz JE, Schuessler RB (2000) Connexin-40, bundle-branch block, and propagation at the Purkinje-myocyte junction. Circ Res 87(10):835-836
15. Yamada KA, Rogers JG, Sundset R, Steinberg TH, Saffitz J (2003) Up-regulation of connexin45 in heart failure. J Cardiovasc Electrophysiol 14(11):1205-1212
16. Gourdie RG, Harfst E, Severs NJ, Green CR (1990) Cardiac gap junctions in rat ventricle: localization using site-directed antibodies and laser scanning confocal microscopy. Cardioscience 1(1):75-82
17. Sepp R, Severs NJ, Gourdie RG (1996) Altered patterns of cardiac intercellular junction distribution in hypertrophic cardiomyopathy. Heart 76(5):412-417
18. Duffy HS (2011) Inflammatory responses in the atria: should they stay or should they go? Heart Rhythm 8(2):286-287. doi: 10.1016/j.hrthm.2010.11.006
19. Martinez-Palomo A, Benitez D, Alanis J (1973) Selective deposition of lanthanum in mammalian cardiac cell membranes. Ultrastructural and electrophysiological evidence. J Cell Biol 58(1):1-10
20. Kohl P (2003) Heterogeneous cell coupling in the heart: an electrophysiological role for fibroblasts. Circ Res 93(5):381-383. doi: 10.1161/01.RES.0000091364.90121.0C
21. Kohl P, Gourdie RG (2014) Fibroblast-myocyte electrotonic coupling: does it occur in native cardiac tissue? J Mol Cell Cardiol 70:37-46. doi: 10.1016/j.yjmcc.2013.12.024
22. Gaudesius G, Miragoli M, Thomas SP, Rohr S (2003) Coupling of cardiac electrical activity over extended distances by fibroblasts of cardiac origin. Circ Res 93(5):421-428. doi: 10.1161/01.RES.0000089258.40661.0C
23. Rook MB, Jongsma HJ, de Jonge B (1989) Single channel currents of homo- and heterologous gap junctions between cardiac fibroblasts and myocytes. Pflugers Arch 414(1):95-98
24. Baum J, Duffy HS (2011) Fibroblasts and myofibroblasts: what are we talking about? J Cardiovasc Pharmacol 57(4):376-379. doi: 10.1097/FJC.0b013e3182116e39
25. Duffy HS (2011) Fibroblasts, myofibroblasts, and fibrosis: fact, fiction, and the future. J Cardiovasc Pharmacol 57(4):373-375. doi: 10.1097/FJC.0b013e3182155a38
26. Green CR, Severs NJ (1984) Connexon rearrangement in cardiac gap junctions: evidence for cytoskeletal control? Cell Tissue Res 237(1):185-186
27. Kleber AG, Saffitz JE (2014) Role of the intercalated disc in cardiac propagation and arrhythmogenesis. Front Physiol 5:404. doi: 10.3389/fphys.2014.00404
28. Dhein S, Seidel T, Salameh A, Jozwiak J, Hagen A, Kostelka M, Hindricks G, Mohr FW (2014) Remodeling of cardiac passive electrical properties and susceptibility to ventricular and atrial arrhythmias. Front Physiol 5:424. doi: 10.3389/fphys.2014.00424
29. Weidmann S (1952) The electrical constants of Purkinje fibres. J Physiol 118(3):348-360
30. Harris AL (2001) Emerging issues of connexin channels: biophysics fills the gap. Q Rev Biophys 34(3):325-472
31. Spach MS, Heidlage JF (1995) The stochastic nature of cardiac propagation at a microscopic level. Electrical description of myocardial architecture and its application to conduction. Circ Res 76(3):366-380
32. Spach MS, Barr RC (2000) Effects of cardiac microstructure on propagating electrical waveforms. Circ Res 86(2):E23-E28
33. Herron TJ, Lee P, Jalife J (2012) Optical imaging of voltage and calcium in cardiac cells & tissues. Circ Res 110(4):609-623. doi: 10.1161/CIRCRESAHA.111.247494
34. Luke RA, Beyer EC, Hoyt RH, Saffitz JE (1989) Quantitative analysis of intercellular connections by immunohistochemistry of the cardiac gap junction protein connexin43. Circ Res 65(5):1450-1457
35. Dun W, Boyden PA (2008) The Purkinje cell; 2008 style. J Mol Cell Cardiol 45(5):617-624. doi: 10.1016/j.yjmcc.2008.08.001
36. Desplantez T, Dupont E, Severs NJ, Weingart R (2007) Gap junction channels and cardiac impulse propagation. J Membr Biol 218(1-3):13-28. doi: 10.1007/s00232-007-9046-8
37. Moreno AP (2004) Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins. Cardiovasc Res 62(2):276-286. doi: 10.1016/j.cardiores.2004.03.003
38. Kwak BR, Hermans MM, De Jonge HR, Lohmann SM, Jongsma HJ, Chanson M (1995) Differential regulation of distinct types of gap junction channels by similar phosphorylating conditions. Mol Biol Cell 6(12):1707-1719
39. Verheule S, van Kempen MJ, te Welscher PH, Kwak BR, Jongsma HJ (1997) Characterization of gap junction channels in adult rabbit atrial and ventricular myocardium. Circ Res 80(5):673-681
40. Lin X, Xu Q, Veenstra RD (2014) Functional formation of heterotypic gap junction channels by connexins-40 and -43. Channels (Austin) 8(5):433-443. doi: 10.4161/19336950.2014.949188
41. Beauchamp P, Yamada KA, Baertschi AJ, Green K, Kanter EM, Saffitz JE, Kleber AG (2006) Relative contributions of connexins 40 and 43 to atrial impulse propagation in synthetic strands of neonatal and fetal murine cardiomyocytes. Circ Res 99(11):1216-1224. doi: 10.1161/01.RES.0000250607.34498.b4
42. Herve JC, Bourmeyster N, Sarrouilhe D, Duffy HS (2007) Gap junctional complexes: from partners to functions. Prog Biophys Mol Biol 94(1-2):29-65. doi: 10.1016/j.pbiomolbio.2007.03.010
43. Giepmans BN, Hengeveld T, Postma FR, Moolenaar WH (2001) Interaction of c-Src with gap junction protein connexin-43. Role in the regulation of cell-cell communication. J Biol Chem 276(11):8544-8549. doi: 10.1074/jbc.M005847200
44. Giepmans BN, Verlaan I, Hengeveld T, Janssen H, Calafat J, Falk MM, Moolenaar WH (2001) Gap junction protein connexin-43 interacts directly with microtubules. Curr Biol 11(17):1364-1368
45. Sovari AA, Iravanian S, Dolmatova E, Jiao Z, Liu H, Zandieh S, Kumar V, Wang K, Bernstein KE, Bonini MG, Duffy HS, Dudley SC (2011) Inhibition of c-Src tyrosine kinase prevents angiotensin II-mediated connexin-43 remodeling and sudden cardiac death. J Am Coll Cardiol 58(22):2332-2339. doi: 10.1016/j.jacc.2011.07.048
46. George CH, Kendall JM, Evans WH (1999) Intracellular trafficking pathways in the assembly of connexins into gap junctions. J Biol Chem 274(13):8678-8685
47. Evans WH, Ahmad S, Diez J, George CH, Kendall JM, Martin PE (1999) Trafficking pathways leading to the formation of gap junctions. Novartis Found Symp 219:44-54 (discussion 54-49)
48. Falk MM (2000) Biosynthesis and structural composition of gap junction intercellular membrane channels. Eur J Cell Biol 79(8):564-574. doi: 10.1078/0171-9335-00080
49. Musil LS, Goodenough DA (1993) Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER. Cell 74(6):1065-1077
50. Schubert AL, Schubert W, Spray DC, Lisanti MP (2002) Connexin family members target to lipid raft domains and interact with caveolin-1. Biochemistry 41(18):5754-5764
51. Shaw RM, Fay AJ, Puthenveedu MA, von Zastrow M, Jan YN, Jan LY (2007) Microtubule plus-end-tracking proteins target gap junctions directly from the cell interior to adherens junctions. Cell 128(3):547-560. doi: 10.1016/j.cell.2006.12.037
52. Smyth JW, Vogan JM, Buch PJ, Zhang SS, Fong TS, Hong TT, Shaw RM (2012) Actin cytoskeleton rest stops regulate anterograde traffic of connexin 43 vesicles to the plasma membrane. Circ Res 110(7):978-989. doi: 10.1161/CIRCRESAHA.111.257964
53. Musil LS, Goodenough DA (1991) Biochemical analysis of connexin43 intracellular transport, phosphorylation, and assembly into gap junctional plaques. J Cell Biol 115(5):1357-1374
54. Su V, Hoang C, Geerts D, Lau AF (2014) CIP75 (connexin43-interacting protein of 75 kDa) mediates the endoplasmic reticulum dislocation of connexin43. Biochem J 458(1):57-67. doi: 10.1042/BJ20131247
55. Smyth JW, Zhang SS, Sanchez JM, Lamouille S, Vogan JM, Hesketh GG, Hong T, Tomaselli GF, Shaw RM (2014) A 14-3-3 mode-1 binding motif initiates gap junction internalization during acute cardiac ischemia. Traffic 15(6):684-699. doi: 10.1111/tra.12169
56. Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Hori M, Tada M (1998) Direct association of the gap junction protein connexin-43 with ZO-1 in cardiac myocytes. J Biol Chem 273(21):12725-12731
57. Barker RJ, Price RL, Gourdie RG (2002) Increased association of ZO-1 with connexin43 during remodeling of cardiac gap junctions. Circ Res 90(3):317-324
58. Hunter AW, Barker RJ, Zhu C, Gourdie RG (2005) Zonula occludens-1 alters connexin43 gap junction size and organization by influencing channel accretion. Mol Biol Cell 16(12):5686-5698. doi: 10.1091/mbc.E05-08-0737
59. Toyofuku T, Yabuki M, Otsu K, Kuzuya T, Tada M, Hori M (1999) Functional role of c-Src in gap junctions of the cardiomyopathic heart. Circ Res 85(8):672-681
60. Duffy HS, Ashton AW, O'Donnell P, Coombs W, Taffet SM, Delmar M, Spray DC (2004) Regulation of connexin43 protein complexes by intracellular acidification. Circ Res 94(2):215-222. doi: 10.1161/01.RES.0000113924.06926.11
61. Sorgen PL, Duffy HS, Sahoo P, Coombs W, Delmar M, Spray DC (2004) Structural changes in the carboxyl terminus of the gap junction protein connexin43 indicates signaling between binding domains for c-Src and zonula occludens-1. J Biol Chem 279(52):54695-54701. doi: 10.1074/jbc.M409552200
62. Rutledge CA, Ng FS, Sulkin MS, Greener ID, Sergeyenko AM, Liu H, Gemel J, Beyer EC, Sovari AA, Efimov IR, Dudley SC (2014) c-Src kinase inhibition reduces arrhythmia inducibility and connexin43 dysregulation after myocardial infarction. J Am Coll Cardiol 63(9):928-934. doi: 10.1016/j.jacc.2013.10.081
63. Rhett JM, Ongstad EL, Jourdan J, Gourdie RG (2012) Cx43 associates with Na(v)1.5 in the cardiomyocyte perinexus. J Membr Biol 245(7):411-422. doi: 10.1007/s00232-012-9465-z
64. Malhotra JD, Thyagarajan V, Chen C, Isom LL (2004) Tyrosine-phosphorylated and nonphosphorylated sodium channel beta1 subunits are differentially localized in cardiac myocytes. J Biol Chem 279(39):40748-40754. doi: 10.1074/jbc.M407243200
65. Sato PY, Coombs W, Lin X, Nekrasova O, Green KJ, Isom LL, Taffet SM, Delmar M (2011) Interactions between ankyrin-G, Plakophilin-2, and Connexin43 at the cardiac intercalated disc. Circ Res 109(2):193-201. doi: 10.1161/CIRCRESAHA.111.247023
66. Oxford EM, Musa H, Maass K, Coombs W, Taffet SM, Delmar M (2007) Connexin43 remodeling caused by inhibition of plakophilin-2 expression in cardiac cells. Circ Res 101(7):703-711. doi: 10.1161/CIRCRESAHA.107.154252
67. Sato PY, Musa H, Coombs W, Guerrero-Serna G, Patino GA, Taffet SM, Isom LL, Delmar M (2009) Loss of plakophilin-2 expression leads to decreased sodium current and slower conduction velocity in cultured cardiac myocytes. Circ Res 105(6):523-526. doi: 10.1161/CIRCRESAHA.109.201418
68. Delmar M (2012) Connexin43 regulates sodium current; ankyrin-G modulates gap junctions: the intercalated disc exchanger. Cardiovasc Res 93(2):220-222. doi: 10.1093/cvr/cvr343
69. Lampe PD, Cooper CD, King TJ, Burt JM (2006) Analysis of Connexin43 phosphorylated at S325, S328 and S330 in normoxic and ischemic heart. J Cell Sci 119(Pt 16):3435-3442. doi: 10.1242/jcs.03089
70. Lampe PD, Lau AF (2004) The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol 36(7):1171-1186. doi: 10.1016/S1357-2725(03)00264-4
71. Morel S, Kwak BR (2012) Roles of connexins in atherosclerosis and ischemia-reperfusion injury. Curr Pharm Biotechnol 13(1):17-26
72. Kadle R, Zhang JT, Nicholson BJ (1991) Tissue-specific distribution of differentially phosphorylated forms of Cx43. Mol Cell Biol 11(1):363-369
73. Lau AF, Hatch-Pigott V, Crow DS (1991) Evidence that heart connexin43 is a phosphoprotein. J Mol Cell Cardiol 23(6):659-663
74. Zhou L, Kasperek EM, Nicholson BJ (1999) Dissection of the molecular basis of pp60(v-src) induced gating of connexin 43 gap junction channels. J Cell Biol 144(5):1033-1045
75. Hyrc K, Rose B (1990) The action of v-src on gap junctional permeability is modulated by pH. J Cell Biol 110(4):1217-1226
76. Arellano RO, Rivera A, Ramon F (1990) Protein phosphorylation and hydrogen ions modulate calcium-induced closure of gap junction channels. Biophys J 57(2):363-367. doi: 10.1016/S0006-3495(90)82537-6
77. Solan JL, Marquez-Rosado L, Sorgen PL, Thornton PJ, Gafken PR, Lampe PD (2007) Phosphorylation at S365 is a gatekeeper event that changes the structure of Cx43 and prevents down-regulation by PKC. J Cell Biol 179(6):1301-1309. doi: 10.1083/jcb.200707060
78. Duthe F, Plaisance I, Sarrouilhe D, Herve JC (2001) Endogenous protein phosphatase 1 runs down gap junctional communication of rat ventricular myocytes. Am J Physiol Cell Physiol 281(5):C1648-C1656
79. Kang M, Lin N, Li C, Meng Q, Zheng Y, Yan X, Deng J, Ou Y, Zhang C, He J, Luo D (2014) Cx43 phosphorylation on S279/282 and intercellular communication are regulated by IP 3/IP 3 receptor signaling. Cell Commun Signal 12(1):58. doi: 10.1186/s12964-014-0058-6
80. Kang M, Lin N, Li C, Meng Q, Zheng Y, Yan X, Deng J, Ou Y, Zhang C, He J, Luo D (2014) Cx43 phosphorylation on S279/282 and intercellular communication are regulated by IP3/IP3 receptor signaling. Cell Commun Signal 12:58. doi: 10.1186/s12964-014-0058-6
81. Rasminsky M (1980) Ephaptic transmission between single nerve fibres in the spinal nerve roots of dystrophic mice. J Physiol 305:151-169
82. Kamermans M, Fahrenfort I (2004) Ephaptic interactions within a chemical synapse: hemichannel-mediated ephaptic inhibition in the retina. Curr Opin Neurobiol 14(5):531-541. doi: 10.1016/j.conb.2004.08.016
83. Beauchamp P, Choby C, Desplantez T, de Peyer K, Green K, Yamada KA, Weingart R, Saffitz JE, Kleber AG (2004) Electrical propagation in synthetic ventricular myocyte strands from germline connexin43 knockout mice. Circ Res 95(2):170-178. doi: 10.1161/01.RES.0000134923.05174.2f
84. Veeraraghavan R, Lin J, Hoeker GS, Keener JP, Gourdie RG, Poelzing S (2015) Sodium channels in the Cx43 gap junction perinexus may constitute a cardiac ephapse: an experimental and modeling study. Pflugers Arch. doi: 10.1007/s00424-014-1675-z
85. Lin J, Keener JP (2013) Ephaptic coupling in cardiac myocytes. IEEE Trans Biomed Eng 60(2):576-582. doi: 10.1109/TBME.2012.2226720
86. Sridharan M, Adderley SP, Bowles EA, Egan TM, Stephenson AH, Ellsworth ML, Sprague RS (2010) Pannexin 1 is the conduit for low oxygen tension-induced ATP release from human erythrocytes. Am J Physiol Heart Circ Physiol 299(4):H1146-H1152. doi: 10.1152/ajpheart.00301.2010
87. Kienitz MC, Bender K, Dermietzel R, Pott L, Zoidl G (2011) Pannexin 1 constitutes the large conductance cation channel of cardiac myocytes. J Biol Chem 286(1):290-298. doi: 10.1074/jbc.M110.163477
88. Dolmatova E, Spagnol G, Boassa D, Baum JR, Keith K, Ambrosi C, Kontaridis MI, Sorgen PL, Sosinsky GE, Duffy HS (2012) Cardiomyocyte ATP release through pannexin 1 aids in early fibroblast activation. Am J Physiol Heart Circ Physiol 303(10):H1208-H1218. doi: 10.1152/ajpheart.00251.2012
89. Vikstrom KL, Vaidyanathan R, Levinsohn S, O'Connell RP, Qian Y, Crye M, Mills JH, Anumonwo JM (2009) SAP97 regulates Kir2.3 channels by multiple mechanisms. Am J Physiol Heart Circ Physiol 297(4):H1387-H1397. doi: 10.1152/ajpheart.00638.2008
90. Gillet L, Rougier JS, Shy D, Sonntag S, Mougenot N, Essers M, Shmerling D, Balse E, Hatem SN, Abriel H (2015) Cardiac-specific ablation of synapse-associated protein SAP97 in mice decreases potassium currents but not sodium current. Heart Rhythm 12(1):181-192. doi: 10.1016/j.hrthm.2014.09.057
91. Kwak BR, Mulhaupt F, Veillard N, Gros DB, Mach F (2002) Altered pattern of vascular connexin expression in atherosclerotic plaques. Arterioscler Thromb Vasc Biol 22(2):225-230
92. Alonso F, Krattinger N, Mazzolai L, Simon A, Waeber G, Meda P, Haefliger JA (2010) An angiotensin II- and NF-kappaB-dependent mechanism increases connexin 43 in murine arteries targeted by renin-dependent hypertension. Cardiovasc Res 87(1):166-176. doi: 10.1093/cvr/cvq031
93. Ko YS, Coppen SR, Dupont E, Rothery S, Severs NJ (2001) Regional differentiation of desmin, connexin43, and connexin45 expression patterns in rat aortic smooth muscle. Arterioscler Thromb Vasc Biol 21(3):355-364
94. Jobs A, Schmidt K, Schmidt VJ, Lubkemeier I, van Veen TA, Kurtz A, Willecke K, de Wit C (2012) Defective Cx40 maintains Cx37 expression but intact Cx40 is crucial for conducted dilations irrespective of hypertension. Hypertension 60(6):1422-1429. doi: 10.1161/HYPERTENSIONAHA.112.201194
95. Boittin FX, Alonso F, Le Gal L, Allagnat F, Beny JL, Haefliger JA (2013) Connexins and M3 muscarinic receptors contribute to heterogeneous Ca(2+) signaling in mouse aortic endothelium. Cell Physiol Biochem 31(1):166-178. doi: 10.1159/000343358
96. Kameritsch P, Pogoda K, Ritter A, Munzing S, Pohl U (2012) Gap junctional communication controls the overall endothelial calcium response to vasoactive agonists. Cardiovasc Res 93(3):508-515. doi: 10.1093/cvr/cvr345
97. Alonso F, Boittin FX, Beny JL, Haefliger JA (2010) Loss of connexin40 is associated with decreased endothelium-dependent relaxations and eNOS levels in the mouse aorta. Am J Physiol Heart Circ Physiol 299(5):H1365-H1373. doi: 10.1152/ajpheart.00029.2010
98. Le Gal L, Alonso F, Wagner C, Germain S, Nardelli Haefliger D, Meda P, Haefliger JA (2014) Restoration of connexin 40 (Cx40) in Renin-producing cells reduces the hypertension of Cx40 null mice. Hypertension 63(6):1198-1204. doi: 10.1161/HYPERTENSIONAHA.113.02976
99. Chadjichristos CE, Scheckenbach KE, van Veen TA, Richani Sarieddine MZ, de Wit C, Yang Z, Roth I, Bacchetta M, Viswambharan H, Foglia B, Dudez T, van Kempen MJ, Coenjaerts FE, Miquerol L, Deutsch U, Jongsma HJ, Chanson M, Kwak BR (2010) Endothelial-specific deletion of connexin40 promotes atherosclerosis by increasing CD73-dependent leukocyte adhesion. Circulation 121(1):123-131. doi: 10.1161/CIRCULATIONAHA.109.867176
100. Pfenniger A, Derouette JP, Verma V, Lin X, Foglia B, Coombs W, Roth I, Satta N, Dunoyer-Geindre S, Sorgen P, Taffet S, Kwak BR, Delmar M (2010) Gap junction protein Cx37 interacts with endothelial nitric oxide synthase in endothelial cells. Arterioscler Thromb Vasc Biol 30(4):827-834. doi: 10.1161/ATVBAHA.109.200816
101. Griffith TM, Chaytor AT, Taylor HJ, Giddings BD, Edwards DH (2002) cAMP facilitates EDHF-type relaxations in conduit arteries by enhancing electrotonic conduction via gap junctions. Proc Natl Acad Sci USA 99(9):6392-6397. doi: 10.1073/pnas.092089799
102. Tang EH, Vanhoutte PM (2008) Gap junction inhibitors reduce endothelium-dependent contractions in the aorta of spontaneously hypertensive rats. J Pharmacol Exp Ther 327(1):148-153. doi: 10.1124/jpet.108.140046
103. Davies PF, Civelek M, Fang Y, Fleming I (2013) The atherosusceptible endothelium: endothelial phenotypes in complex haemodynamic shear stress regions in vivo. Cardiovasc Res 99(2):315-327. doi: 10.1093/cvr/cvt101
104. Meens MJ, Pfenniger A, Kwak BR, Delmar M (2013) Regulation of cardiovascular connexins by mechanical forces and junctions. Cardiovasc Res 99(2):304-314. doi: 10.1093/cvr/cvt095
105. Gabriels JE, Paul DL (1998) Connexin43 is highly localized to sites of disturbed flow in rat aortic endothelium but connexin37 and connexin40 are more uniformly distributed. Circ Res 83(6):636-643
106. Cowan DB, Lye SJ, Langille BL (1998) Regulation of vascular connexin43 gene expression by mechanical loads. Circ Res 82(7):786-793
107. DePaola N, Davies PF, Pritchard WF Jr, Florez L, Harbeck N, Polacek DC (1999) Spatial and temporal regulation of gap junction connexin43 in vascular endothelial cells exposed to controlled disturbed flows in vitro. Proc Natl Acad Sci USA 96(6):3154-3159
108. Kwak BR, Silacci P, Stergiopulos N, Hayoz D, Meda P (2005) Shear stress and cyclic circumferential stretch, but not pressure, alter connexin43 expression in endothelial cells. Cell Commun Adhes 12(5-6):261-270. doi: 10.1080/15419060500514119
109. Pfenniger A, Wong C, Sutter E, Cuhlmann S, Dunoyer-Geindre S, Mach F, Horrevoets AJ, Evans PC, Krams R, Kwak BR (2012) Shear stress modulates the expression of the atheroprotective protein Cx37 in endothelial cells. J Mol Cell Cardiol 53(2):299-309. doi: 10.1016/j.yjmcc.2012.05.011
110. Wong CW, Christen T, Roth I, Chadjichristos CE, Derouette JP, Foglia BF, Chanson M, Goodenough DA, Kwak BR (2006) Connexin37 protects against atherosclerosis by regulating monocyte adhesion. Nat Med 12(8):950-954. doi: 10.1038/nm1441
111. Wong CW, Burger F, Pelli G, Mach F, Kwak BR (2003) Dual benefit of reduced Cx43 on atherosclerosis in LDL receptor-deficient mice. Cell Commun Adhes 10(4-6):395-400
112. Kwak BR, Veillard N, Pelli G, Mulhaupt F, James RW, Chanson M, Mach F (2003) Reduced connexin43 expression inhibits atherosclerotic lesion formation in low-density lipoprotein receptor-deficient mice. Circulation 107(7):1033-1039
113. Yeh HI, Lupu F, Dupont E, Severs NJ (1997) Upregulation of connexin43 gap junctions between smooth muscle cells after balloon catheter injury in the rat carotid artery. Arterioscler Thromb Vasc Biol 17(11):3174-3184
114. Chadjichristos CE, Matter CM, Roth I, Sutter E, Pelli G, Luscher TF, Chanson M, Kwak BR (2006) Reduced connexin43 expression limits neointima formation after balloon distension injury in hypercholesterolemic mice. Circulation 113(24):2835-2843. doi: 10.1161/CIRCULATIONAHA.106.627703
115. Liao Y, Regan CP, Manabe I, Owens GK, Day KH, Damon DN, Duling BR (2007) Smooth muscle-targeted knockout of connexin43 enhances neointimal formation in response to vascular injury. Arterioscler Thromb Vasc Biol 27(5):1037-1042. doi: 10.1161/ATVBAHA.106.137182
116. Song M, Yu X, Cui X, Zhu G, Zhao G, Chen J, Huang L (2009) Blockade of connexin 43 hemichannels reduces neointima formation after vascular injury by inhibiting proliferation and phenotypic modulation of smooth muscle cells. Exp Biol Med (Maywood) 234(10):1192-1200. doi: 10.3181/0902-RM-80
117. Lohman AW, Billaud M, Straub AC, Johnstone SR, Best AK, Lee M, Barr K, Penuela S, Laird DW, Isakson BE (2012) Expression of pannexin isoforms in the systemic murine arterial network. J Vasc Res 49(5):405-416. doi: 10.1159/000338758
118. Gaynullina D, Tarasova OS, Kiryukhina OO, Shestopalov VI, Panchin Y (2014) Endothelial function is impaired in conduit arteries of pannexin1 knockout mice. Biol Direct 9:8. doi: 10.1186/1745-6150-9-8
119. Storkebaum E, Ruiz de Almodovar C, Meens M, Zacchigna S, Mazzone M, Vanhoutte G, Vinckier S, Miskiewicz K, Poesen K, Lambrechts D, Janssen GM, Fazzi GE, Verstreken P, Haigh J, Schiffers PM, Rohrer H, Van der Linden A, De Mey JG, Carmeliet P (2010) Impaired autonomic regulation of resistance arteries in mice with low vascular endothelial growth factor or upon vascular endothelial growth factor trap delivery. Circulation 122(3):273-281. doi: 10.1161/CIRCULATIONAHA.109.929364
120. Christensen KL, Mulvany MJ (2001) Location of resistance arteries. J Vasc Res 38(1):1-12. doi: 10.1159/000051024
121. Sandow SL, Senadheera S, Bertrand PP, Murphy TV, Tare M (2012) Myoendothelial contacts, gap junctions, and microdomains: anatomical links to function? Microcirculation 19(5):403-415. doi: 10.1111/j.1549-8719.2011.00146.x
122. Haddock RE, Grayson TH, Brackenbury TD, Meaney KR, Neylon CB, Sandow SL, Hill CE (2006) Endothelial coordination of cerebral vasomotion via myoendothelial gap junctions containing connexins 37 and 40. Am J Physiol Heart Circ Physiol 291(5):H2047-H2056. doi: 10.1152/ajpheart.00484.2006
123. Isakson BE, Best AK, Duling BR (2008) Incidence of protein on actin bridges between endothelium and smooth muscle in arterioles demonstrates heterogeneous connexin expression and phosphorylation. Am J Physiol Heart Circ Physiol 294(6):H2898-H2904. doi: 10.1152/ajpheart.91488.2007
124. Sandow SL, Neylon CB, Chen MX, Garland CJ (2006) Spatial separation of endothelial small- and intermediate-conductance calcium-activated potassium channels (KCa) and connexins: possible relationship to vasodilator function? J Anat 209(5):689-698. doi: 10.1111/j.1469-7580.2006.00647.x
125. Beny JL, Schaad O (2000) An evaluation of potassium ions as endothelium-derived hyperpolarizing factor in porcine coronary arteries. Br J Pharmacol 131(5):965-973. doi: 10.1038/sj.bjp.0703658
126. Edwards G, Dora KA, Gardener MJ, Garland CJ, Weston AH (1998) K+ is an endothelium-derived hyperpolarizing factor in rat arteries. Nature 396(6708):269-272. doi: 10.1038/24388
127. Hutcheson IR, Chaytor AT, Evans WH, Griffith TM (1999) Nitric oxide-independent relaxations to acetylcholine and A23187 involve different routes of heterocellular communication. Role of Gap junctions and phospholipase A2. Circ Res 84(1):53-63
128. Kansui Y, Fujii K, Nakamura K, Goto K, Oniki H, Abe I, Shibata Y, Iida M (2004) Angiotensin II receptor blockade corrects altered expression of gap junctions in vascular endothelial cells from hypertensive rats. Am J Physiol Heart Circ Physiol 287(1):H216-H224. doi: 10.1152/ajpheart.00915.2003
129. Mather S, Dora KA, Sandow SL, Winter P, Garland CJ (2005) Rapid endothelial cell-selective loading of connexin 40 antibody blocks endothelium-derived hyperpolarizing factor dilation in rat small mesenteric arteries. Circ Res 97(4):399-407. doi: 10.1161/01.RES.0000178008.46759.d0
130. Rath G, Saliez J, Behets G, Romero-Perez M, Leon-Gomez E, Bouzin C, Vriens J, Nilius B, Feron O, Dessy C (2012) Vascular hypoxic preconditioning relies on TRPV4-dependent calcium influx and proper intercellular gap junctions communication. Arterioscler Thromb Vasc Biol 32(9):2241-2249. doi: 10.1161/ATVBAHA.112.252783
131. Yamamoto Y, Imaeda K, Suzuki H (1999) Endothelium-dependent hyperpolarization and intercellular electrical coupling in Guinea-pig mesenteric arterioles. J Physiol 514(Pt 2):505-513
132. Dora KA (2010) Coordination of vasomotor responses by the endothelium. Circ J 74(2):226-232
133. Howitt L, Chaston DJ, Sandow SL, Matthaei KI, Edwards FR, Hill CE (2013) Spreading vasodilatation in the murine microcirculation: attenuation by oxidative stress-induced change in electromechanical coupling. J Physiol 591(Pt 8):2157-2173. doi: 10.1113/jphysiol.2013.250928
134. Dora KA, Xia J, Duling BR (2003) Endothelial cell signaling during conducted vasomotor responses. Am J Physiol Heart Circ Physiol 285(1):H119-H126. doi: 10.1152/ajpheart.00643.2002
135. Figueroa XF, Duling BR (2008) Dissection of two Cx37-independent conducted vasodilator mechanisms by deletion of Cx40: electrotonic versus regenerative conduction. Am J Physiol Heart Circ Physiol 295(5):H2001-H2007. doi: 10.1152/ajpheart.00063.2008
136. Wolfle SE, de Wit C (2005) Intact endothelium-dependent dilation and conducted responses in resistance vessels of hypercholesterolemic mice in vivo. J Vasc Res 42(6):475-482. doi: 10.1159/000088101
137. de Wit C, Roos F, Bolz SS, Pohl U (2003) Lack of vascular connexin 40 is associated with hypertension and irregular arteriolar vasomotion. Physiol Genomics 13(2):169-177. doi: 10.1152/physiolgenomics.00169.2002
138. de Wit C, Roos F, Bolz SS, Kirchhoff S, Kruger O, Willecke K, Pohl U (2000) Impaired conduction of vasodilation along arterioles in connexin40-deficient mice. Circ Res 86(6):649-655
139. 2+-dependent proinflammatory responses in lung capillaries. J Clin Invest 116(8):2193-2200. doi: 10.1172/JCI26605
140. Wang L, Yin J, Nickles HT, Ranke H, Tabuchi A, Hoffmann J, Tabeling C, Barbosa-Sicard E, Chanson M, Kwak BR, Shin HS, Wu S, Isakson BE, Witzenrath M, de Wit C, Fleming I, Kuppe H, Kuebler WM (2012) Hypoxic pulmonary vasoconstriction requires connexin 40-mediated endothelial signal conduction. J Clin Invest 122(11):4218-4230. doi: 10.1172/JCI59176
141. Dora KA, Doyle MP, Duling BR (1997) Elevation of intracellular calcium in smooth muscle causes endothelial cell generation of NO in arterioles. Proc Natl Acad Sci USA 94(12):6529-6534
142. Straub AC, Billaud M, Johnstone SR, Best AK, Yemen S, Dwyer ST, Looft-Wilson R, Lysiak JJ, Gaston B, Palmer L, Isakson BE (2011) Compartmentalized connexin 43 s-nitrosylation/denitrosylation regulates heterocellular communication in the vessel wall. Arterioscler Thromb Vasc Biol 31(2):399-407. doi: 10.1161/ATVBAHA.110.215939
143. Figueroa XF, Lillo MA, Gaete PS, Riquelme MA, Saez JC (2013) Diffusion of nitric oxide across cell membranes of the vascular wall requires specific connexin-based channels. Neuropharmacology 75:471-478. doi: 10.1016/j.neuropharm.2013.02.022
144. Theis M, de Wit C, Schlaeger TM, Eckardt D, Kruger O, Doring B, Risau W, Deutsch U, Pohl U, Willecke K (2001) Endothelium-specific replacement of the connexin43 coding region by a lacZ reporter gene. Genesis 29(1):1-13
145. Liao Y, Day KH, Damon DN, Duling BR (2001) Endothelial cell-specific knockout of connexin 43 causes hypotension and bradycardia in mice. Proc Natl Acad Sci USA 98(17):9989-9994. doi: 10.1073/pnas.171305298
146. Krattinger N, Capponi A, Mazzolai L, Aubert JF, Caille D, Nicod P, Waeber G, Meda P, Haefliger JA (2007) Connexin40 regulates renin production and blood pressure. Kidney Int 72(7):814-822. doi: 10.1038/sj.ki.5002423
147. Wagner C, Jobs A, Schweda F, Kurtz L, Kurt B, Lopez ML, Gomez RA, van Veen TA, de Wit C, Kurtz A (2010) Selective deletion of Connexin 40 in renin-producing cells impairs renal baroreceptor function and is associated with arterial hypertension. Kidney Int 78(8):762-768. doi: 10.1038/ki.2010.257
148. Billaud M, Lohman AW, Straub AC, Looft-Wilson R, Johnstone SR, Araj CA, Best AK, Chekeni FB, Ravichandran KS, Penuela S, Laird DW, Isakson BE (2011) Pannexin1 regulates alpha1-adrenergic receptor- mediated vasoconstriction. Circ Res 109(1):80-85. doi: 10.1161/CIRCRESAHA.110.237594
149. Locovei S, Bao L, Dahl G (2006) Pannexin 1 in erythrocytes: function without a gap. Proc Natl Acad Sci USA 103(20):7655-7659. doi: 10.1073/pnas.0601037103
150. Billaud M, Chiu YH, Lohman AW, Parpaite T, Butcher JT, Mutchler SM, DeLalio LJ, Artamonov MV, Sandilos JK, Best AK, Somlyo AV, Thompson RJ, Le TH, Ravichandran KS, Bayliss DA, Isakson BE (2015) A molecular signature in the pannexin1 intracellular loop confers channel activation by the alpha1 adrenoreceptor in smooth muscle cells. Sci Signal 8(364):ra17. doi: 10.1126/scisignal.2005824
151. Angus JA, Betrie AH, Wright CE (2015) Pannexin-1 channels do not regulate alpha-adrenoceptor-mediated vasoconstriction in resistance arteries. Eur J Pharmacol. doi: 10.1016/j.ejphar.2015.01.024
152. Gaete PS, Lillo MA, Figueroa XF (2014) Functional role of connexins and pannexins in the interaction between vascular and nervous system. J Cell Physiol 229(10):1336-1345. doi: 10.1002/jcp.24563
153. Burns AR, Phillips SC, Sokoya EM (2012) Pannexin protein expression in the rat middle cerebral artery. J Vasc Res 49(2):101-110. doi: 10.1159/000332329
154. Kutkut I, Meens MJ, McKee TA, Bochaton-Piallat ML, Kwak BR (2015) Lymphatic vessels: an emerging actor in atherosclerotic plaque development. Eur J Clin Invest 45(1):100-108. doi: 10.1111/eci.12372
155. Krenacs T, Rosendaal M (1995) Immunohistological detection of gap junctions in human lymphoid tissue: connexin43 in follicular dendritic and lymphoendothelial cells. J Histochem Cytochem 43(11):1125-1137
156. Compton CC, Raviola E (1985) Structure of the sinus-lining cells in the popliteal lymph node of the rabbit. Anat Rec 212(4):408-423. doi: 10.1002/ar.1092120412
157. Sabine A, Agalarov Y, Maby-El Hajjami H, Jaquet M, Hagerling R, Pollmann C, Bebber D, Pfenniger A, Miura N, Dormond O, Calmes JM, Adams RH, Makinen T, Kiefer F, Kwak BR, Petrova TV (2012) Mechanotransduction, PROX1, and FOXC2 cooperate to control connexin37 and calcineurin during lymphatic-valve formation. Dev Cell 22(2):430-445. doi: 10.1016/j.devcel.2011.12.020
158. Kanady JD, Dellinger MT, Munger SJ, Witte MH, Simon AM (2011) Connexin37 and Connexin43 deficiencies in mice disrupt lymphatic valve development and result in lymphatic disorders including lymphedema and chylothorax. Dev Biol 354(2):253-266. doi: 10.1016/j.ydbio.2011.04.004
159. Benoit JN, Zawieja DC, Goodman AH, Granger HJ (1989) Characterization of intact mesenteric lymphatic pump and its responsiveness to acute edemagenic stress. Am J Physiol 257(6 Pt 2):H2059-H2069
160. Munger SJ, Kanady JD, Simon AM (2013) Absence of venous valves in mice lacking Connexin37. Dev Biol 373(2):338-348. doi: 10.1016/j.ydbio.2012.10.032
161. Meens MJ, Sabine A, Petrova TV, Kwak BR (2014) Connexins in lymphatic vessel physiology and disease. FEBS Lett 588(8):1271-1277. doi: 10.1016/j.febslet.2014.01.011
162. Agullo-Pascual E, Cerrone M, Delmar M (2014) Arrhythmogenic cardiomyopathy and Brugada syndrome: diseases of the connexome. FEBS Lett 588(8):1322-1330. doi: 10.1016/j.febslet.2014.02.008
163. Veeraraghavan R, Poelzing S, Gourdie RG (2014) Old cogs, new tricks: a scaffolding role for connexin43 and a junctional role for sodium channels? FEBS Lett 588(8):1244-1248. doi: 10.1016/j.febslet.2014.01.026
164. Bouvier D, Kieken F, Kellezi A, Sorgen PL (2008) Structural changes in the carboxyl terminus of the gap junction protein connexin 40 caused by the interaction with c-Src and zonula occludens-1. Cell Commun Adhes 15(1):107-118. doi: 10.1080/15419060802014347