Modulation of Cx46 hemichannels by nitric oxide
| Autor: | ShengYong Yin, Luis Reuss, Mauricio A. Retamal, Guillermo A. Altenberg |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Cell signaling
Physiology Recombinant Fusion Proteins Connexin Nitric Oxide Cataract Connexins Permeability Membrane Potentials S-Nitrosoglutathione Xenopus laevis chemistry.chemical_compound Animals Nitric Oxide Donors Cysteine Ion channel Fluorescent Dyes Chemistry Gap junction Gap Junctions Cell Biology S-Nitrosylation Rats Dithiothreitol Kinetics Transmembrane domain Biochemistry Reducing Agents Connexin 43 Mutation Oocytes Biophysics Membrane Transporters Ion Channels and Pumps Ion Channel Gating Oxidation-Reduction Intracellular |
| Zdroj: | AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY Artículos CONICYT CONICYT Chile instacron:CONICYT |
| ISSN: | 1522-1563 0363-6143 |
| DOI: | 10.1152/ajpcell.00054.2009 |
| Popis: | Gap-junction hemichannels are composed of six protein subunits (connexins). Undocked hemichannels contribute to physiological autocrine/paracrine cell signaling, including release of signaling molecules, cell-volume regulation, and glucose uptake. In addition, hemichannels may be pathologically activated by dephosphorylation and cell-membrane depolarization. Such hemichannel opening may induce and/or accelerate cell death. It has been suggested that connexin43 (Cx43) hemichannels are sensitive to redox potential changes and that one or more intracellular cysteines is/are important for this process. Cx46 is expressed in the lens, and its dysfunction induces cataract formation. It contains six cysteines in the extracellular loops, one in the fourth transmembrane helix, and two in the COOH-terminal domain. The latter may be susceptible to oxidation by nitric oxide (NO), which could be involved in cataract formation through cysteine S-nitrosylation. Here we report studies of the effects of the NO donor S-nitrosoglutathione (GSNO) on the electrical properties and fluorescent-dye permeability of wild-type Cx46 and mutant hemichannels expressed in Xenopus laevis oocytes. GSNO enhanced hemichannel voltage sensitivity, increased tail-current amplitude, and changed activation and closing kinetics in Cx46 and Cx46-CT43 (Cx46 mutant in which the COOH terminus was replaced with that of Cx43), but not in Cx46-C3A (Cx46 in which the intracellular and transmembrane helix 4 cysteines were mutated to alanine). We conclude that Cx46 hemichannels are sensitive to NO and that the NO effects are mediated by modification of one or more intracellular cysteines. However, it is unlikely that NO induces cataract formation due to the hemichannel activation, because at normal resting potential, NO had no major effects on Cx46 hemichannel permeability. |
| Databáze: | OpenAIRE |
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