The connexin channel pore: Pore-lining segments and residues

Connexins: A Guide

Volumn , Issue , 2009, Pages 77-102

  Verselis, Vytas K ^a  

^a ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

Author keywords

Conductance; Cx26; Cx32; Cx37; Cx40; Cx43; Cx46; Cysteine scanning accessibility mutagenesis; Gap junction; Hemichannel; Pore; Selectivity

Indexed keywords

EID: 66749104885     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-59745-489-6_3     Document Type: Chapter

References (64)

1. Harris AL. Emerging issues of connexin channels: biophysics fills the gap. Q Rev Biophys. 2001;34:325-472.
2. Alexander DB, Goldberg GS. Transfer of biologically important molecules between cells through gap junction channels. Curr Med Chem. 2003;10:2045-58.
3. Neijssen J, Herberts C, Drijfhout JW, Reits E, Janssen L, Neefjes J. Cross-presentation by intercellular peptide transfer through gap junctions. Nature. 2005;434:83-8.
4. Valiunas V, Polosina YY, Miller H, Potapova IA, Valiuniene L, Doronin S, Mathias RT, Robinson RB, Rosen MR, Cohen IS, Brink PR. Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions. J Physiol. 2005;568:459-68.
5. Goldberg GS, Valiunas V, Brink PR. Selective permeability of gap junction channels. Biochim Biophys Acta. 2004;1662:96-101.
6. Weber PA, Chang HC, Spaeth KE, Nitsche JM, Nicholson BJ. The permeability of gap junction channels to probes of different size is dependent on connexin composition and permeant-pore affinities. Biophys J. 2004;87:958-73.
7. Bevans CG, Kordel M, Rhee SK, Harris AL. Isoform composition of connexin channels determines selectivity among second messengers and uncharged molecules. J Biol Chem. 1998;273:2808-16.
8. Ayad WA, Locke D, Koreen IV, Harris AL. Heteromeric, but not homomeric, connexin channels are selectively permeable to inositol phosphates. J Biol Chem. 2006;281:16727-39.
9. Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R. The structure of the potassium channel: molecular basis of K+ conduction and selectivity. Science. 1998;280:69-77.
10. + channel. Nature. 2003;423:33-41.
11. Long SB, Campbell EB, Mackinnon R. Crystal structure of a mammalian voltagedependent Shaker family K+ channel. Science. 2005;309:897-903.
12. Noskov SY, Roux B. Ion selectivity in potassium channels. Biophys Chem. 2006;124:279-91.
13. Unger VM, Kumar NM, Gilula NB, Yeager M. Three-dimensional structure of a recombinant gap junction membrane channel. Science. 1999;283:1176-80.
14. Oshima A, Tani K, Hiroaki Y, Fujiyoshi Y, Sosinsky GE. Three-dimensional structure of a human connexin26 gap junction channel reveals a plug in the vestibule. Proc Natl Acad Sci USA. 2007;104:10034-9
15. Ghoshroy S, Goodenough DA, Sosinsky GE. Preparation, characterization, and structure of half gap junctional layers split with urea and EGTA. J Membr Biol. 1995;146:15-28.
16. Müller DJ, Hand GM, Engel A, Sosinsky GE. Conformational changes in surface structures of isolated connexin 26 gap junctions. EMBO J. 2002;21:3598-607.
17. Thimm J, Mechler A, Lin H, Rhee S, Lal R. Calcium-dependent open/closed conformations and interfacial energy maps of reconstituted hemichannels. J Biol Chem. 2005;280:10646-54.
18. Fleishman SJ, Unger VM, Yeager M, Ben-Tal N. A C-α model for the transmembrane α helices of gap junction intercellular channels. Mol Cell. 2004;15:879-88.
19. Long SB, Campbell EB, Mackinnon R. Voltage sensor of Kv1.2: structural basis of electromechanical coupling. Science. 2005;309:903-8.
20. Tombola F, Pathak MM, Isacoff EY. How does voltage open an ion channel? Annu Rev Cell Dev Biol. 2006;22:23-52.
21. Spray DC, Harris AL, Bennett MVL. Equilibrium properties of a voltage-dependent junctional conductance. J Gen Physiol. 1981;77:77-93.
22. Bukauskas FF, Verselis VK. Gap junction channel gating. Biochim Biophys Acta. 2004;1662:42-60.
23. Harris AL, Spray DC, Bennett MVL. Kinetic properties of a voltage-dependent junctional conductance. J Gen Physiol. 1981;77:95-117.
24. Verselis VK, Bennett MVL, Bargiello TA. A voltage-dependent gap junction in Drosophila melanogaster. Biophys J. 1991;59:114-26.
25. Weingart R, Bukauskas FF. Gap junction channels of insects exhibit a residual conductance. Pflügers Arch. 1993;424:192-4.
26. Moreno AP, Rook MB, Fishman GI, Spray DC. Gap junction channels: distinct voltagesensitive and - insensitive conductance states. Biophys J. 1994;67:113-9.
27. Trexler EB, Bennett MVL, Bargiello TA, Verselis VK. Voltage-gating and permeation in a gap junction hemichannel. Proc Natl Acad Sci USA. 1996;93:5836-41.
28. Verselis VK, Ginter CS, Bargiello TA. Opposite voltage-gating polarities of two closely related connexins. Nature. 1994;368:348-51.
29. Oh S, Abrams CK, Verselis VK, Bargiello TA. Stoichiometry of transjunctional voltagegating polarity reversal by a negative charge substitution in the amino terminus of a connexin32 chimera. J Gen Physiol. 2000;116:13-31.
30. Purnick PE, Benjamin DC, Verselis VK, Bargiello TA, Dowd TL. Structure of the amino terminus of a gap junction protein. Arch Biochem Biophys. 2000;381:181-90.
31. Purnick PE, Oh S, Abrams CK, Verselis VK, Bargiello TA. Reversal of the gating polarity of gap junctions by negative charge substitutions in the N-terminus of connexin 32. Biophys J. 2000;79:2403-15.
32. Oh S, Rivkin S, Tang Q, Verselis VK, Bargiello TA. Determinants of gating polarity of a connexin 32 hemichannel. Biophys J. 2004;87:912-28.
33. Musa H, Fenn E, Crye M, Gemel J, Beyer EC, Veenstra RD. Amino terminal glutamate residues confer spermine sensitivity and affect voltage-gating and channel conductance of rat connexin40 gap junctions. J Physiol. 2004;557:863-78.
34. Tong JJ, Ebihara L. Structural determinants for the differences in voltage-gating of chicken Cx56 and Cx45.6 gap-junctional hemichannels. Biophys J. 2006;91:2142-54.
35. Pfahnl A, Zhou XW, Werner R, Dahl G. A chimeric connexin forming gap junction hemichannels. Pflügers Arch. 1997;433:773-9.
36. Trexler EB, Bukauskas FF, Kronengold J, Bargiello TA, Verselis VK. The first extracellular loop domain is a major determinant of charge selectivity in connexin46 channels. Biophys J. 2000;79:3036-51.
37. Musa H, Veenstra RD. Voltage-dependent blockade of connexin40 gap junctions by spermine. Biophys J. 2003;84:205-19.
38. Hu X, Dahl G. Exchange of conductance and gating properties between gap junction hemichannels. FEBS Lett. 1999;45:113-7.
39. Hu X, Ma M, Dahl G. Conductance of connexin hemichannels segregates with the first transmembrane segment. Biophys J. 2006;90:140-50.
40. Zhou XW, Pfahnl A, Werner R, Hudder A, Llanes A, Luebke A, Dahl G. Identification of a pore-lining segment in gap junction hemichannels. Biophys J. 1997;72:1946-53.
41. Kronengold J, Trexler EB, Bukauskas FF, Bargiello TA, Verselis VK. Single-channel SCAM identifies pore-lining residues in the first extracellular loop and first transmembrane domains of Cx46 hemichannels. J Gen Physiol. 2003;122:389-405.
42. Karlin A, Akabas MH. Substituted-cysteine accessibility method. Meth Enzymol. 1998;293:123-45.
43. Pfahnl A, Dahl G. Localization of a voltage gate in connexin46 gap junction hemichannels. Biophys J. 1998;75:2323-31.
44. Skerrett IM, Aronowitz J, Shin JH, Cymes G, Kasperek E, Cao FL, Nicholson BJ. Identification of amino acid residues lining the pore of a gap junction channel. J Cell Biol. 2002;159:349-60.
45. Bennett MVL, Zheng X, Sogin ML. The connexins and their family tree. Soc Gen Physiol Ser. 1994;49:223-33.
46. Cruciani V, Mikalsen SO. Evolutionary selection pressure and family relationships among connexin genes. Biol Chem. 2007;388:253-64.
47. Valiunas V, Weingart R. Electrical properties of gap junction hemichannels identified in transfected HeLa cells. Pflügers Arch. 2000;440:366-79.
48. Bukauskas FF, Kreuzberg MM, Rackauskas M, Bukauskiene A, Bennett MV, Verselis VK, Willecke K. Properties of mouse connexin 30.2 and human connexin 31.9 hemichannels: implications for atrioventricular conduction in the heart. Proc Natl Acad Sci USA. 2006;103:9726-31.
49. Beahm DL, Hall JE. Hemichannel and junctional properties of connexin 50. Biophys J. 2002;82:2016-31.
50. Srinivas M, Kronengold J, Bukauskas FF, Bargiello TA, Verselis VK. Correlative studies of gating in Cx46 and Cx50 hemichannels and gap junction channels. Biophys J. 2005;88:1725-39.
51. Bukauskas FF, Bukauskiene A, Bennett MVL, Verselis VK. Gating properties of gap junction channels assembled from connexin43 and connexin43 fused with green fluorescent protein. Biophys J. 2001;81:137-52.
52. Contreras JE, Sá ez JC, Bukauskas FF, Bennett MVL. Functioning of cx43 hemichannels demonstrated by single channel properties. Cell Commun Adhes. 2003;10:245-9.
53. Trexler EB, Bukauskas FF, Bennett MVL, Bargiello TA, Verselis VK. Rapid and direct effects of pH on connexins revealed by the connexin46 hemichannel preparation. J Gen Physiol. 1999;113:721-42.
54. Ebihara L, Steiner E. Properties of a nonjunctional current expressed from a rat connexin46 cDNA in Xenopus oocytes. J Gen Physiol. 1993;102:59-74.
55. Srinivas M, Calderon DP, Kronengold J, Verselis VK. Regulation of connexin hemichannels by monovalent cations. J Gen Physiol. 2006;127:67-75.
56. Valiunas V. Biophysical properties of connexin-45 gap junction hemichannels studied in vertebrate cells. J Gen Physiol. 2002;119:147-64.
57. Kaneko S, Akaike A, Satoh M. Cut-open recording techniques. Meth Enzymol. 1998;293:319-31.
58. Bera AK, Chatav M, Akabas MH. GABA (A) receptor M2-M3 loop secondary structure and changes in accessibility during channel gating. J Biol Chem. 2002;277:43002-10.
59. Kronengold J, Trexler EB, Bukauskas FF, Bargiello TA, Verselis VK. Pore-lining residues identified by single channel SCAM studies in Cx46 hemichannels. Cell Commun Adhes. 2003;10:193-9.
60. Dahl G, Levine E, Rabadan Diehl C, Werner R. Cell/cell channel formation involves disulfide exchange. Eur J Biochem. 1991;197:141-4.
61. Foote CI, Zhou L, Zhu X, Nicholson BJ. The pattern of disulfide linkages in the extracellular loop regions of connexin 32 suggests a model for the docking interface of gap junctions. J Cell Biol. 1998;140:1187-97.
62. Bao X, Chen Y, Reuss L, Altenberg GA. Functional expression in Xenopus oocytes of gap-junctional hemichannels formed by a cysteine-less connexin 43. J Biol Chem. 2004;279:9689-92.
63. Chang G, Spencer RH, Lee AT, Barclay MT, Rees DC. Structure of the MscL homolog from Mycobacterium tuberculosis: a gated mechanosensitive ion channel. Science. 1998;282:2220-6.
64. Miyazawa A, Fujiyoshi Y, Unwin N. Structure and gating mechanism of the acetylcholine receptor pore. Nature. 2003;423:949-55.