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Intracellular calcium changes trigger connexin 32 hemichannel opening.
Elke De Vuyst1, Elke Decrock, Liesbet Cabooter
1Department of Physiology and Pathophysiology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium.
The EMBO Journal
|December 13, 2005
Summary
Increased cytoplasmic calcium concentration ([Ca2+]i) triggers connexin hemichannel opening, leading to ATP release and dye uptake. This finding suggests physiological control over hemichannel activity.
Area of Science:
- Cellular Biology
- Biophysics
Background:
- Connexin hemichannels facilitate extracellular messenger release, but physiological triggers remain unknown.
- Previous studies relied on indirect evidence like connexin expression and gap junction blockers.
Purpose of the Study:
- To investigate if elevated cytoplasmic calcium concentration ([Ca2+]i) acts as a physiological trigger for connexin hemichannel opening.
- To elucidate the role of calcium in regulating hemichannel activity.
Main Methods:
- Utilized connexin 32 (Cx32)-expressing cells.
- Employed specific Cx32 mimetic peptides to block hemichannels.
- Measured ATP release and dye uptake.
- Manipulated intracellular calcium levels and used a calmodulin antagonist.
Main Results:
- Increased [Ca2+]i triggered ATP release and dye uptake in Cx32-expressing cells.
- These effects were dependent on Cx32 expression and blocked by Cx32 mimetic peptides.
- Calmodulin antagonism and specific [Ca2+]i elevation (around 500 nM) were critical.
- Cx43 mimetic peptides did not block the observed effects.
Conclusions:
- Elevated cytoplasmic calcium concentration ([Ca2+]i) is a direct trigger for connexin hemichannel opening.
- Connexin hemichannels are under physiological control mediated by intracellular calcium.
- Cx32 hemichannels are specifically implicated in this calcium-dependent release pathway.