Biophys J, December 1999, p. 2968-2987, Vol. 77, No. 6

Different Ionic Selectivities for Connexins 26 and 32 Produce Rectifying Gap Junction Channels

 ^*Department of Biological Sciences and  ^#Department of Chemical Engineering, SUNY at Buffalo, Buffalo, New York 14260;  ^§Department of Pharmacology, SUNY Health Science Center, Syracuse, New York 13210; and  ^¶Department of Biophysics, Johns Hopkins University, Baltimore, Maryland 21218 USA

The functional diversity of gap junction intercellular channels arising from the large number of connexin isoforms is significantly increased by heterotypic interactions between members of this family. This is particularly evident in the rectifying behavior of Cx26/Cx32 heterotypic channels (Barrio et al., 1991. Proc. Natl. Acad. Sci. USA. 88:8410-8414). The channel properties responsible for producing the rectifying current observed for Cx26/Cx32 heterotypic gap junction channels were determined in transfected mouse neuroblastoma 2A (N2A) cells. Transfectants revealed maximum unitary conductances (_j) of 135 pS for Cx26 and 53 pS for Cx32 homotypic channels in 120 mM KCl. Anionic substitution of glutamate for Cl indicated that Cx26 channels favored cations by 2.6:1, whereas Cx32 channels were relatively nonselective with respect to charge. In Cx26/Cx32 heterotypic cell pairs, the macroscopic fast rectification of the current-voltage relationship was fully explained at the single-channel level by a rectifying _j that increased by a factor of 2.9 as the transjunctional voltage (V_j) changed from 100 to +100 mV with the Cx26 cell as the positive pole. A model of electrodiffusion of ions through the gap junction pore based on Nernst-Planck equations for ion concentrations and the Poisson equation for the electrical potential within the junction is developed. Selectivity characteristics are ascribed to each hemichannel based on either pore features (treated as uniform along the length of the hemichannel) or entrance effects unique to each connexin. Both analytical GHK approximations and full numerical solutions predict rectifying characteristics for Cx32/Cx26 heterotypic channels, although not to the full extent seen empirically. The model predicts that asymmetries in the conductance/permeability properties of the hemichannels (also cast as Donnan potentials) will produce either an accumulation or a depletion of ions within the channel, depending on voltage polarity, that will result in rectification.

Biophys J, December 1999, p. 2968-2987, Vol. 77, No. 6
© 1999 by the Biophysical Society   0006-3495/99/12/2968/20  $2.00

This article has been cited by other articles:

				G. Mese, V. Valiunas, P. R. Brink, and T. W. White Connexin26 deafness associated mutations show altered permeability to large cationic molecules Am J Physiol Cell Physiol, October 1, 2008; 295(4): C966 - C974. [Abstract] [Full Text] [PDF]

				G. Kanaporis, G. Mese, L. Valiuniene, T. W. White, P. R. Brink, and V. Valiunas Gap Junction Channels Exhibit Connexin-specific Permeability to Cyclic Nucleotides J. Gen. Physiol., March 31, 2008; 131(4): 293 - 305. [Abstract] [Full Text] [PDF]

				D. Gonzalez, J. M. Gomez-Hernandez, and L. C. Barrio Species specificity of mammalian connexin-26 to form open voltage-gated hemichannels FASEB J, November 1, 2006; 20(13): 2329 - 2338. [Abstract] [Full Text] [PDF]

				K. Maass, A. Ghanem, J.-S. Kim, M. Saathoff, S. Urschel, G. Kirfel, R. Grummer, M. Kretz, T. Lewalter, K. Tiemann, et al. Defective Epidermal Barrier in Neonatal Mice Lacking the C-Terminal Region of Connexin43 Mol. Biol. Cell, October 1, 2004; 15(10): 4597 - 4608. [Abstract] [Full Text] [PDF]

				P. A. Weber, H.-C. Chang, K. E. Spaeth, J. M. Nitsche, and B. J. Nicholson The Permeability of Gap Junction Channels to Probes of Different Size Is Dependent on Connexin Composition and Permeant-Pore Affinities Biophys. J., August 1, 2004; 87(2): 958 - 973. [Abstract] [Full Text] [PDF]

				D. Locke, I. V. Koreen, J. Y. Liu, and A. L. Harris Reversible Pore Block of Connexin Channels by Cyclodextrins J. Biol. Chem., May 28, 2004; 279(22): 22883 - 22892. [Abstract] [Full Text] [PDF]

				J. M. Nitsche, H.-C. Chang, P. A. Weber, and B. J. Nicholson A Transient Diffusion Model Yields Unitary Gap Junctional Permeabilities from Images of Cell-to-Cell Fluorescent Dye Transfer Between Xenopus Oocytes Biophys. J., April 1, 2004; 86(4): 2058 - 2077. [Abstract] [Full Text] [PDF]

				B. J. Nicholson Gap junctions - from cell to molecule J. Cell Sci., November 15, 2003; 116(22): 4479 - 4481. [Full Text] [PDF]

				I.M. Skerrett, J. Aronowitz, J.H. Shin, G. Cymes, E. Kasperek, F.L. Cao, and B.J. Nicholson Identification of amino acid residues lining the pore of a gap junction channel J. Cell Biol., October 28, 2002; 159(2): 349 - 360. [Abstract] [Full Text] [PDF]

				M. Kamermans, I. Fahrenfort, K. Schultz, U. Janssen-Bienhold, T. Sjoerdsma, and R. Weiler Hemichannel-Mediated Inhibition in the Outer Retina Science, May 11, 2001; 292(5519): 1178 - 1180. [Abstract] [Full Text]