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Calcium binding and voltage gating in Cx46 hemichannels
- Source :
- Scientific Reports, Artículos CONICYT, CONICYT Chile, instacron:CONICYT, Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
- Publication Year :
- 2016
-
Abstract
- The opening of connexin (Cx) hemichannels in the membrane is tightly regulated by calcium (Ca2+) and membrane voltage. Electrophysiological and atomic force microscopy experiments indicate that Ca2+ stabilizes the hemichannel closed state. However, structural data show that Ca2+ binding induces an electrostatic seal preventing ion transport without significant structural rearrangements. In agreement with the closed-state stabilization hypothesis, we found that the apparent Ca2+ sensitivity is increased as the voltage is made more negative. Moreover, the voltage and Ca2+ dependence of the channel kinetics indicate that the voltage sensor movement and Ca2+ binding are allosterically coupled. An allosteric kinetic model in which the Ca2+ decreases the energy necessary to deactivate the voltage sensor reproduces the effects of Ca2+ and voltage in Cx46 hemichannels. In agreement with the model and suggesting a conformational change that narrows the pore, Ca2+ inhibits the water flux through Cx hemichannels. We conclude that Ca2+ and voltage act allosterically to stabilize the closed conformation of Cx46 hemichannels.
- Subjects :
- 0301 basic medicine
Conformational change
Allosteric regulation
chemistry.chemical_element
Connexin
lcsh:Medicine
Gating
Calcium
Microscopy, Atomic Force
Connexins
Article
Membrane Potentials
03 medical and health sciences
Xenopus laevis
Animals
Humans
Calcium Signaling
lcsh:Science
Ion transporter
Membrane potential
Multidisciplinary
Chemistry
lcsh:R
Rats
Electrophysiology
Kinetics
030104 developmental biology
Biophysics
Oocytes
lcsh:Q
Calcium Channels
Subjects
Details
- ISSN :
- 20452322
- Volume :
- 7
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Scientific reports
- Accession number :
- edsair.doi.dedup.....558c2fd7780e113f2b9c052fe34905fe