Connexins regulate calcium signaling by controlling ATP release
M L Cotrina1, J H Lin, A Alves-Rodrigues
1Departments of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 10595, USA.
Summary
Connexin expression enhances ATP secretion, which drives intercellular calcium waves in cell lines. This signaling relies on ATP release, not increased cell-to-cell coupling, challenging previous assumptions.
Area of Science:
- Cell biology
- Biochemistry
- Neuroscience
Background:
- Gap junctions, formed by connexins, facilitate direct cell-to-cell communication.
- Intercellular calcium waves are crucial signaling events in various biological processes.
- Previous understanding suggested gap junction coupling was primary for calcium wave propagation.
Purpose of the Study:
- To investigate the mechanism by which connexin expression influences intercellular calcium wave propagation.
- To determine the role of ATP secretion and purinergic signaling in connexin-mediated calcium waves.
- To re-evaluate the contribution of direct gap junction coupling versus paracrine signaling.
Main Methods:
- Forced expression of connexins in gap junction-deficient cell lines (C6 glioma, HeLa, U373 glioblastoma).
- Measurement of ATP secretion and intracellular calcium mobilization.
- Assessment of calcium wave propagation using purinergic receptor antagonists and chloride channel blockers.
Main Results:
- Connexin expression potentiated ATP secretion 5- to 15-fold in tested cell lines.
- ATP release was dependent on purinergic receptor activation and intracellular calcium.
- Calcium wave propagation was reduced by purinergic antagonists and Cl- channel blockers, but not gap junction inhibitors.
Conclusions:
- Connexin expression enhances intercellular calcium waves primarily through increased ATP secretion.
- Paracrine signaling via released ATP, mediated by purinergic receptors, is the key mechanism.
- The findings challenge the established view that direct gap junction coupling is the main driver of these signaling events.
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