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10:46
Mechanical Stimulation-induced Calcium Wave Propagation in Cell Monolayers: The Example of Bovine Corneal Endothelial Cells
Published on: July 16, 2013
The intercellular synchronization of Ca2+ oscillations evaluates Cx36-dependent coupling.
Sabine Bavamian1, Helena Pontes, José Cancela
1Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, Geneva, Switzerland. sabine@broadinstitute.org
Plos One
|August 1, 2012
Summary
Researchers developed a new assay to screen for drugs targeting Connexin36 (Cx36) channels, crucial for insulin secretion. This method identifies compounds that modulate Cx36-dependent cell coupling and calcium signaling in beta cells.
Area of Science:
- Cellular biology
- Neuroscience
- Endocrinology
Background:
- Connexin36 (Cx36) is vital for synchronized calcium (Ca2+) signaling in insulin secretion.
- A lack of specific drugs targeting Cx36 channels hinders research into its precise role.
Purpose of the Study:
- To develop and validate a novel assay for screening drugs that modulate Cx36 channel activity.
- To identify new therapeutic agents impacting beta-cell function, neuronal communication, and related cell types.
Main Methods:
- Developed a semi-automatic, fluorimetric assay for quantifying Ca2+ transients in MIN6 cell populations.
- Utilized MIN6 cells with altered Cx36 expression/function to validate the assay.
- Tested known drugs (glibenclamide, quinine) and screened novel compounds for effects on Ca2+ synchronization and Cx36 coupling.
Main Results:
- Reduced Cx36 expression/function decreased glucose-induced Ca2+ oscillation synchrony.
- Glibenclamide enhanced Cx36 coupling and cell synchrony; quinine inhibited it.
- Identified multiple drugs altering Ca2+ synchronization, cell coupling, Cx36 distribution, and insulin content.
Conclusions:
- Intercellular Ca2+ oscillation synchrony is a reliable, non-invasive measure of Cx36-dependent coupling.
- The developed assay effectively identifies novel drugs affecting Cx36-mediated functions in beta-cells and neurons.
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