Connexin37 Forms High Conductance Gap Junction Channels with Subconductance State Activity and Selective Dye and Ionic Permeabilities

Overview

Journal Biophys J

Publisher Cell Press

Specialty Biophysics

Date 1994 Jun 1

PMID 7521227

Citations 49

Authors

R D Veenstra

H Z Wang

E C Beyer

S V Ramanan

P R Brink

Affiliations

Soon will be listed here.

Abstract

Gap junctions are thought to mediate the direct intercellular coupling of adjacent cells by the open-closed gating of an aqueous pore permeable to ions and molecules of up to 1 kDa or 10-14 A in diameter. We symmetrically altered the ionic composition or asymmetrically added 6-carboxyfluorescein (6-CF, M(r) = 376), a fluorescent tracer, to pairs of connexin37-transfected mouse neuro2A cells to examine the ionic and dye permeability of human connexin37 channels. We demonstrate that the 300-pS channel formed by connexin37 has an effective relative anion/cation permeability ratio of 0.43, directly converts to at least one intermediate (63 pS) subconductance state, and that 6-CF dye transfer is accompanied by a 24% decrease in unitary channel conductance. These observations favor a new interpretation of the gap junction pore consistent with direct ion-channel interactions or electrostatic charge effects common to more conventional multistate ion channels. These results have distinct implications about the different forms of intercellular signaling (cationic, ionic, and/or biochemical) that can occur depending on the expression and conformation of the connexin channel proteins.

Citing Articles

The Hydrophobic Residues in Amino Terminal Domains of Cx46 and Cx50 Are Important for Their Gap Junction Channel Ion Permeation and Gating.

Jaradat R, Li X, Chen H, Stathopulos P, Bai D Int J Mol Sci. 2022; 23(19).

PMID: 36232905 PMC: 9570504. DOI: 10.3390/ijms231911605.

Connexin 46 and connexin 50 gap junction channel properties are shaped by structural and dynamic features of their N-terminal domains.

Yue B, Haddad B, Khan U, Chen H, Atalla M, Zhang Z J Physiol. 2021; 599(13):3313-3335.

PMID: 33876426 PMC: 8249348. DOI: 10.1113/JP281339.

Connexins in Cardiovascular and Neurovascular Health and Disease: Pharmacological Implications.

Leybaert L, Lampe P, Dhein S, Kwak B, Ferdinandy P, Beyer E Pharmacol Rev. 2017; 69(4):396-478.

PMID: 28931622 PMC: 5612248. DOI: 10.1124/pr.115.012062.

Stochastic Model of Gap Junctions Exhibiting Rectification and Multiple Closed States of Slow Gates.

Snipas M, Kraujalis T, Paulauskas N, Maciunas K, Bukauskas F Biophys J. 2016; 110(6):1322-33.

PMID: 27028642 PMC: 4816716. DOI: 10.1016/j.bpj.2016.01.035.

Reverberation of excitation in neuronal networks interconnected through voltage-gated gap junction channels.

Maciunas K, Snipas M, Paulauskas N, Bukauskas F J Gen Physiol. 2016; 147(3):273-88.

PMID: 26880752 PMC: 4772373. DOI: 10.1085/jgp.201511488.

References

Bukauskas F, Kempf C, Weingart R . Electrical coupling between cells of the insect Aedes albopictus. J Physiol. 1992; 448:321-37. PMC: 1176202. DOI: 10.1113/jphysiol.1992.sp019044. View

Rubin J, Verselis V, Bennett M, Bargiello T . Molecular analysis of voltage dependence of heterotypic gap junctions formed by connexins 26 and 32. Biophys J. 1992; 62(1):183-93; discussion 193-5. PMC: 1260515. DOI: 10.1016/S0006-3495(92)81804-0. View

Moreno A, Fishman G, Spray D . Phosphorylation shifts unitary conductance and modifies voltage dependent kinetics of human connexin43 gap junction channels. Biophys J. 1992; 62(1):51-3. PMC: 1260481. DOI: 10.1016/S0006-3495(92)81775-7. View

Chen Y, Dehaan R . Multiple-channel conductance states and voltage regulation of embryonic chick cardiac gap junctions. J Membr Biol. 1992; 127(2):95-111. DOI: 10.1007/BF00233282. View

Hennemann H, SCHWARZ H, Willecke K . Characterization of gap junction genes expressed in F9 embryonic carcinoma cells: molecular cloning of mouse connexin31 and -45 cDNAs. Eur J Cell Biol. 1992; 57(1):51-8. View

Veenstra R, Wang H, Westphale E, Beyer E . Multiple connexins confer distinct regulatory and conductance properties of gap junctions in developing heart. Circ Res. 1992; 71(5):1277-83. DOI: 10.1161/01.res.71.5.1277. View

Rup D, Veenstra R, Wang H, Brink P, Beyer E . Chick connexin-56, a novel lens gap junction protein. Molecular cloning and functional expression. J Biol Chem. 1993; 268(1):706-12. View

Reed K, Westphale E, Larson D, Wang H, Veenstra R, Beyer E . Molecular cloning and functional expression of human connexin37, an endothelial cell gap junction protein. J Clin Invest. 1993; 91(3):997-1004. PMC: 288052. DOI: 10.1172/JCI116321. View

Mantz J, Cordier J, Giaume C . Effects of general anesthetics on intercellular communications mediated by gap junctions between astrocytes in primary culture. Anesthesiology. 1993; 78(5):892-901. DOI: 10.1097/00000542-199305000-00014. View

10.

Ramanan S, Brink P . Multichannel recordings from membranes which contain gap junctions. II. Substates and conductance shifts. Biophys J. 1993; 65(4):1387-95. PMC: 1225865. DOI: 10.1016/S0006-3495(93)81193-7. View

11.

Chen Y, Dehaan R . Temperature dependence of embryonic cardiac gap junction conductance and channel kinetics. J Membr Biol. 1993; 136(2):125-34. DOI: 10.1007/BF02505757. View

12.

Eisenman G . Cation selective glass electrodes and their mode of operation. Biophys J. 1962; 2(2 Pt 2):259-323. PMC: 1366487. DOI: 10.1016/s0006-3495(62)86959-8. View

13.

Tsien R, Weingart R . Inotropic effect of cyclic AMP in calf ventricular muscle studied by a cut end method. J Physiol. 1976; 260(1):117-41. PMC: 1309080. DOI: 10.1113/jphysiol.1976.sp011507. View

14.

Simpson I, Rose B, Loewenstein W . Size limit of molecules permeating the junctional membrane channels. Science. 1977; 195(4275):294-6. DOI: 10.1126/science.831276. View

15.

Simpson I, Loewenstein W . Permeability of the cell-to-cell membrane channels in mammalian cell juncton. Science. 1979; 205(4404):404-7. DOI: 10.1126/science.377490. View

16.

Brink P, DEWEY M . Evidence for fixed charge in the nexus. Nature. 1980; 285(5760):101-2. DOI: 10.1038/285101a0. View

17.

Schwarzmann G, Wiegandt H, Rose B, Zimmerman A, Loewenstein W . Diameter of the cell-to-cell junctional membrane channels as probed with neutral molecules. Science. 1981; 213(4507):551-3. DOI: 10.1126/science.7244653. View

18.

Dahl G, Loewenstein W . Cell junction and cyclic AMP: 1. Upregulation of junctional membrane permeability and junctional membrane particles by administration of cyclic nucleotide or phosphodiesterase inhibitor. J Membr Biol. 1981; 63(1-2):105-21. DOI: 10.1007/BF01969452. View

19.

Makowski L, Caspar D, Phillips W, Goodenough D . Gap junction structures. V. Structural chemistry inferred from X-ray diffraction measurements on sucrose accessibility and trypsin susceptibility. J Mol Biol. 1984; 174(3):449-81. DOI: 10.1016/0022-2836(84)90331-0. View

20.

Neyton J, Trautmann A . Single-channel currents of an intercellular junction. Nature. 1985; 317(6035):331-5. DOI: 10.1038/317331a0. View