Heteromultimeric Gap Junction Channels: A Connection With Cardiac Physiology and Pathology

  • Alonso P. Moreno
  • Guoqiang Zhong
  • Volodya Hayrapetyan
Chapter
Part of the Basic Science for the Cardiologist book series (BASC, volume 12)

Abstract

Growing evidence that heteromultimeric channels are formedin vivosuggests that junctional communication is not only governed by the permeability and gating mechanism of gap junctions formed by one type of connexin, but also by the interaction of multiple subunits that form channels (Loewenstein1981; Ramon and Riveral986). Despite our current limited knowledge about interaction among cardiac connexins, it has become necessary to review and interpret how combinations of connexin subunits participate in the physiology and pathology of electrical and metabolic transmission in the heart.

Keywords

Xenopus Oocyte Unitary Conductance Junctional Communication Functional Channel Heteromeric Channel 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Reference

  1. Anumonwo J.M., Taffet S., Gu H., Chanson M., Moreno A.P., Delmar M. (2001). The carboxyl terminal domain regulates the unitary conductance and voltage dependence of connexin40 gap junction channels. Circ Res 88, 666–673.PubMedCrossRefGoogle Scholar
  2. Barrio L.C., Suchyna T., Bargiello T., Xu X., Roginski R., Bennett M.V.L., Nicholson B.J. (1991). Voltage dependence of homo-and hetero-typic Cx26 and Cx32 gap junctions expressed in Xenopus oocytes. Proc Nat! Acad Sci USA 88, 8410–8414.CrossRefGoogle Scholar
  3. Beyer E.C., Paul D.L., Goodenough D.A. (1990). Connexin family of gap junction proteins. J Membr Biol 116, 187–194.PubMedCrossRefGoogle Scholar
  4. Brink P.R., Cronin K., Banach K., Peterson E., Westphale E.M., Seul K.H., Ramanan S.V., Beyer E.C. (1997). Evidence for heteromeric gap junction channels formed from rat connexin43 and human connexin37. Am J Physiol 273, C1386–96.PubMedGoogle Scholar
  5. Coppen S.R., Kodama I., Boyett M.R., Dobrzynski H., Takagishi Y., Honjo H., Yeh, HI, Severs N.J. (1999a). Connexin45, a major connexin of the rabbit sinoatrial node, is co-expressed with connexin43 in a restricted zone at the nodal-crista term inalis border. J Histochem Cytochem 47, 907–918.PubMedCrossRefGoogle Scholar
  6. Coppen S.R., Severs N.J., Gourdie R.G. (1999b). Connexin45 (alpha6) Expression Delineates an Extended Conduction System in the Embryonic and Mature Rodent Heart. Devel Genetics 24, 82–90.CrossRefGoogle Scholar
  7. Delorme B., Dahl E., Jarry-Guichard T., Briand J.P., Willecke K., TheveniauRuissy M., Gros D. (1997). Expression pattern of connexin gene products at the early developmental stages of the mouse cardiovascular system. Cire Res 81, 423–437.CrossRefGoogle Scholar
  8. Eghbali B., Kessler J.A., Spray D.C. (1990). Expression of gap junction channels in communication-incompetent cells after stable transfection with cDNA encoding connexin 32. Proc Natl Acad Sci USA 87, 1328–1331.PubMedCrossRefGoogle Scholar
  9. Elenes S, Martinez AD, Beyer EC, Moreno AP. Heterotypic docking of Cx43 and Cx45 connexons blocks fast voltage gating of Cx43. Biophys J 81, 1406–1418. 2001.PubMedCrossRefGoogle Scholar
  10. Elenes S., Rubart M., Moreno A.P. (1999). Junctional communication between isolated pairs of canine atrial cells is mediated by homogeneous and heterogeneous gap junction channels. J Cardiovasc Electrophys 10, 990–1004.CrossRefGoogle Scholar
  11. Gu H., Ek-Vitorin J.F., Taffet S.M., Delmar M. (2000). Coexpression of connexins 40 and 43 enhances the pH sensitivity of gap junctions: a model for synergistic interactions among connexins. Cire Res (Online) 86, E98–E103.CrossRefGoogle Scholar
  12. Gutstein D.E., Morley G.E., Tamaddon H., Vaidya D., Schneider M.D., Chen J., Chien K.R., Stuhlmann H., Fishman G.I. (2001). Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43. Circ Res 88, 333–339.PubMedCrossRefGoogle Scholar
  13. He D.S., Jiang J.X., Taffet S.M., Burt J.M. (1999). Formation of heteromeric gap junction channels by connexins 40 and 43 in vascular smooth muscle cells. Proc Natl Acad Sci USA 96, 6495–6500.PubMedCrossRefGoogle Scholar
  14. Hopperstad M., Srinivas M., Spray D. (2001). Properties of Gap Junction Channels Formed by Cx46 Alone and in Combination with Cx50. Biophys J 79, 1954–1966.CrossRefGoogle Scholar
  15. Jongsma H.J., Wilders R. (2000). Gap junctions in cardiovascular disease. Circ Res 86, 1193–1197.PubMedCrossRefGoogle Scholar
  16. Kanter H.L., Beyer E.C., Saffitz J.E. (1995). Structural and molecular determinants of intercellular coupling in cardiac myocytes. Microscopy Research & Technique 31, 357–363.CrossRefGoogle Scholar
  17. Kirchhoff S., Nelles E., Hagendorff A., Kruger O., Traub O., Willecke K. (1998). Reduced cardiac conduction velocity and predisposition to arrhythmias in connexin40-deficient mice. Current Biology 8, 299–302.PubMedCrossRefGoogle Scholar
  18. Koval M., Geist S.T., Westphale E.M., Kemendy A.E., Civitelli R., Beyer E.C., Steinberg T.H. (1995). Transfected connexin45 alters gap junction permeability in cells expressing endogenous connexin43. J Cell Biol 130, 987–995.PubMedCrossRefGoogle Scholar
  19. Kwak B.R., Saez J.C., Wilders R., Chanson M., Fishman G.I., Hertzberg E.L., Spray D.C., Jongsma H.J. (1995). Effects of cGMP-dependent phosphorylation on rat and human connexin43 gap junction channels. Pflugers Arch 430, 770–778.PubMedCrossRefGoogle Scholar
  20. Kwong K.F., Schuessler R.B., Green K.G., Laing J.G., Beyer E.C., Boineau J.P., Saffitz J.E. (1998). Differential expression of gap junction proteins in the canine sinus node. Circ Res 82, 604–612.PubMedCrossRefGoogle Scholar
  21. Lampe P.D., TenBroek E.M., Burt J.M., Kurata W.E., Johnson R.G. (2000). Phosphorylation of Connexin43 on Serine368 by Protein Kinase C Regulates Gap Junctional Communication. J Cell Biol 149, 1503–1512.PubMedCrossRefGoogle Scholar
  22. Loewenstein W.R. (1981). Junctional intercellular communication: the cell-tocell membrane channel. Physiol Rev 61, 829–913.PubMedGoogle Scholar
  23. Moore L.K., Beyer E.C., Burt J.M. (1991). Characterization of gap junction channels in A7r5 vascular smooth muscle cells. Am J Physiol 260, C975–C981.PubMedGoogle Scholar
  24. Moreno A.P., Eghbali B., Spray D.C. (1991). Connexin32 gap junction channels in stably transfected cells. Equilibrium and kinetic properties. Biophys J 60, 1267–1277.PubMedCrossRefGoogle Scholar
  25. Moreno A.P., Laing J.G., Beyer E.C., Spray D.C. (1995). Properties of gap junction channels formed of connexin 45 endogenously expressed in human hepatoma (SKHep1) cells. Am J Physiol 268, C356–65.PubMedGoogle Scholar
  26. Moreno A.P., Rook M.B., Fishman G.I., Spray D.C. (1994a). Gap junction channels: distinct voltage-sensitive and - insensitive conductance states. Biophys J 67, 113–119.PubMedCrossRefGoogle Scholar
  27. Moreno A.P., Saez J.C., Fishman G.I., Spray D.C. (1994b). Human connexin43 gap junction channels. Regulation of unitary conductances by phosphorylation. Circ Res 74, 1050–1057.PubMedCrossRefGoogle Scholar
  28. Moreno A.P., Chanson M., Anumonwo J., Scerri I., Gu H., Taffet S.M., Delmar M. (2002). Role of the Carboxyl Terminal of Connexin43 in Transjunctional Fast Voltage Gating. Circ Res 90, 450–457PubMedCrossRefGoogle Scholar
  29. Oh S., Abrams C.K., Verselis V.K., Bargiello T.A. (2000). Stoichiometry of transjunctional voltage-gating polarity reversal by a negative charge substitution in the amino terminus of a Cx32 chimera. J Gen Physiol 116, 13–31.PubMedCrossRefGoogle Scholar
  30. Peters N.S. (1996). New insights into myocardial arrhythmogenesis: distribution of gap-junctional coupling in normal, ischaemic and hypertrophied human hearts. Clinical Science 90, 447–452.PubMedGoogle Scholar
  31. Ramon F., Rivera A. (1986). Gap junction channel modulation--a physiological viewpoint. Prog Biophys Mol Biol 48, 127–153.PubMedCrossRefGoogle Scholar
  32. Revilla A., Castro C., Barrio L.C. (1999). Molecular dissection of transjunctional voltage dependence in the connexin-32 and connexin-43 junctions. Biophys J 77, 1374–1383.PubMedCrossRefGoogle Scholar
  33. Rook M.B., Jongsma H.J., de Jonge B. (1989). Single channel currents of homo-and heterologous gap junctions between cardiac fibroblasts and myocytes. Pflugers Arch 414, 95–98.PubMedCrossRefGoogle Scholar
  34. Thomas S.A., Schuessler R.B., Berul Cd., Beardslee M.A., Beyer E.C., Mendelsohn M.E., Saffitz J.E. (1998). Disparate effects of deficient expression of connexin43 on atrial and ventricular conduction: evidence for chamber-specific molecular determinants of conduction. Circulation 97, 686–691.PubMedCrossRefGoogle Scholar
  35. Trabka-Janik E., Coombs W., Lemanski L.F., Delmar M., Jalife, J. (1994). Immunohistochemical localization of gap junction protein channels in hamster sinoatrial node in correlation with electrophysiologic mapping of the pacemaker region. J Cardiovasc Electrophysiol 5, 125–137.PubMedCrossRefGoogle Scholar
  36. Trexler E.B., Verselis V.K. (2001). The study of connexin hemichannels (connexons) in Xenopus oocytes. Methods in Molecular Biology 154, 341–355.Google Scholar
  37. Vaidya D., Tamaddon H.S., Lo C.W., Taffet S.M., Delmar M., Morley G.E., Jalife J. (2001). Null mutation of connexin43 causes slow propagation of ventricular activation in the late stages of mouse embryonic development. Circ Res 88, 1196–1202.PubMedCrossRefGoogle Scholar
  38. Valiunas V., Weingart R., Brink P.R. (2000). Formation of heterotypic gap junction channels by connexins 40 and 43. Circ Res (Online) 86, E42–E49.Google Scholar
  39. van der Velden H.M.W., van der Z.L., Wijffels M.C., van Leuven C., Dorland R., Vos M.A., Jongsma H.J., Allessie M.A. (2000). Atrial fibrillation in the goat induces changes in monophasic action potential and mRNA expression of ion channels involved in repolarization. J Cardiovasc Electrophysiol 11, 1262–1269.PubMedCrossRefGoogle Scholar
  40. van Rijen H.V., van Veen T.A., van Kempen M.J., Wihns-Schopman F.J., Potse M., Krueger O., Willecke K., Opthof T., Jongsma H.J., de Bakker J.M. (2001a). Impaired conduction in the bundle branches of mouse hearts lacking the gap junction protein connodn40. Circulation 103, 1591–1598.PubMedCrossRefGoogle Scholar
  41. van Rijen H.V., Wilders R., Rook M.B., Jongsma H.J. 2001b. Dual patch clamp. Methods in Molecular Biology 154, 269–292.PubMedGoogle Scholar
  42. van Veen T.A., van Rijen H.V., Jongsma H.J. (2000). Electrical conductance of mouse connexin45 gap junction channels is modulated by phosphorylation. Cardiovasc Res 46, 496–510.PubMedCrossRefGoogle Scholar
  43. Veenstra R.D., Wang H.Z., Beblo D.A., Chilton M.G., Harris A.L., Beyer E.C., Brink P.R. (1995). Selectivity of connexin-specific gap junctions does not correlate with channel conductance. Circ Res 77, 1156–1165.PubMedCrossRefGoogle Scholar
  44. Verheule S., van Kempen M.J., Postma S., Rook M.B., Jongsma H.J. (2001). Gap junctions in the rabbit sinoatrial node. Am J Physiol 280, H2103- H2115.Google Scholar
  45. Werner R., Levine E., Rabadan Diehl C., Dahl G. (1991). Gating properties of connexin32 cell-cell channels and their mutants expressed in Xenopus oocytes. Proc R Soc Lond 243, 5–11.CrossRefGoogle Scholar
  46. White T.W., Bruzzone R., Paul D.L. (1995). The connexin family of intercellular channel forming proteins. Kidney International 48, 1148–1157.PubMedCrossRefGoogle Scholar
  47. Wilders R., Kumar R., Joyner R.W., Jongsma H.J., Verheijck E.E., Golod D., van Ginneken A.C., Goolsby W.N. (1996). Action potential conduction between a ventricular cell model and an isolated ventricular cell. Biophys J 70, 281–295.PubMedCrossRefGoogle Scholar
  48. Yeh H.I., Rothery S., Dupont E., Coppen S.R., Severs N.J. (1998). Individual Gap Junction Plaques Contain Multiple Connexins in Arterial Endothelium. Circ Res 83, 1248–1263.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Alonso P. Moreno
    • 1
  • Guoqiang Zhong
    • 1
  • Volodya Hayrapetyan
    • 1
  1. 1.Krannert Inst. of CardiologyIndiana University School of MedicineIndianapolis

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