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J Biol Chem, Vol. 274, Issue 6, 3720-3725, February 5, 1999
From the Thomas C. Jenkins Department of Biophysics, The Johns
Hopkins University, Baltimore, Maryland 21218
Connexin channels mediate molecular communication
between cells. However, positive identification of biological ligands
that directly and noncovalently modulate their activity has been
elusive. This study demonstrates a high affinity inhibition of connexin channels by the purine cyclic monophosphates cAMP and cGMP. Purified homomeric connexin-32 and heteromeric connexin-32/connexin-26 channels
were inhibited by exposure to nanomolar levels of the nucleotides prior
to incorporation into membranes. Access to the site of action, or
affinity for the nucleotides, was greatly reduced following
incorporation of the connexin channels into membranes, where inhibition
required millimolar concentrations of the nucleotides. The high
affinity inhibition did not occur with similar concentrations of AMP,
ADP, ATP, cTMP, or cCMP. This is the first report of a direct ligand
effect on connexin channel function. The high affinity and specificity
of the inhibition suggest a biological role in control of connexin
channels and also may lead to the application of affinity reagents to
study of connexin channel structure-function.
This article has been cited by other articles:
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  L. Tao and A. L. Harris 2-Aminoethoxydiphenyl Borate Directly Inhibits Channels Composed of Connexin26 and/or Connexin32 Mol. Pharmacol., February 1, 2007; 71(2): 570 - 579. [Abstract] [Full Text] [PDF]
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 W. A. Ayad, D. Locke, I. V. Koreen, and A. L. Harris Heteromeric, but Not Homomeric, Connexin Channels Are Selectively Permeable to Inositol Phosphates J. Biol. Chem., June 16, 2006; 281(24): 16727 - 16739. [Abstract] [Full Text] [PDF]
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 V Valiunas, Y. Y Polosina, H Miller, I. A Potapova, L Valiuniene, S Doronin, R. T Mathias, R. B Robinson, M. R Rosen, I. S Cohen, et al. Connexin-specific cell-to-cell transfer of short interfering RNA by gap junctions J. Physiol., October 15, 2005; 568(2): 459 - 468. [Abstract] [Full Text] [PDF]
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L. Tao and A. L. Harris Biochemical Requirements for Inhibition of Connexin26-containing Channels by Natural and Synthetic Taurine Analogs J. Biol. Chem., September 10, 2004; 279(37): 38544 - 38554. [Abstract] [Full Text] [PDF]
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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]
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 A. P Moreno Biophysical properties of homomeric and heteromultimeric channels formed by cardiac connexins Cardiovasc Res, May 1, 2004; 62(2): 276 - 286. [Abstract] [Full Text] [PDF]
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 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]
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G. S. Goldberg, A. P. Moreno, and P. D. Lampe Gap Junctions between Cells Expressing Connexin 43 or 32 Show Inverse Permselectivity to Adenosine and ATP J. Biol. Chem., September 20, 2002; 277(39): 36725 - 36730. [Abstract] [Full Text] [PDF]
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T. A.B. van Veen, H. V.M. van Rijen, and T. Opthof Cardiac gap junction channels: modulation of expression and channel properties Cardiovasc Res, August 1, 2001; 51(2): 217 - 229. [Abstract] [Full Text] [PDF]
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 S. Verheule, M. J. A. van Kempen, S. Postma, M. B. Rook, and H. J. Jongsma Gap junctions in the rabbit sinoatrial node Am J Physiol Heart Circ Physiol, May 1, 2001; 280(5): H2103 - H2115. [Abstract] [Full Text] [PDF]
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 D. S. He and J. M. Burt Mechanism and Selectivity of the Effects of Halothane on Gap Junction Channel Function Circ. Res., June 9, 2000; 86(11): 104e - 109. [Abstract] [Full Text]
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V. Valiunas, R. Weingart, and P. R. Brink Formation of Heterotypic Gap Junction Channels by Connexins 40 and 43 Circ. Res., February 4, 2000; 86(2): 42e - 49. [Abstract] [Full Text]
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C. G. Bevans and A. L. Harris Regulation of Connexin Channels by pH. DIRECT ACTION OF THE PROTONATED FORM OF TAURINE AND OTHER AMINOSULFONATES J. Biol. Chem., February 5, 1999; 274(6): 3711 - 3719. [Abstract] [Full Text] [PDF]
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