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Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling
Published on: August 1, 2016
Cyclic ADP-ribose enhances coupling between voltage-gated Ca2+ entry and intracellular Ca2+ release
1Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, United Kingdom. ruth.empson@pharm.ox.ac.uk
The Journal of Biological Chemistry
|August 22, 1997
Summary
Calcium (Ca2+) release from intracellular stores in neurons is amplified by Ca2+-induced Ca2+ release, involving ryanodine receptors. Cyclic ADP-ribose enhances this process, suggesting a role in neuronal signaling.
Area of Science:
- Neuroscience
- Cellular Biology
- Biochemistry
Background:
- Neuronal activity involves calcium (Ca2+) influx through voltage-gated channels.
- Ca2+ influx can trigger Ca2+ release from intracellular stores, a process known as Ca2+-induced Ca2+ release.
- Ryanodine receptors (RyRs) are key mediators of this Ca2+ release mechanism.
Purpose of the Study:
- To investigate the role of cyclic ADP-ribose (cADPR) in modulating Ca2+-induced Ca2+ release in neurons.
- To determine if cADPR acts as an endogenous modulator of ryanodine receptors in neuronal cells.
Main Methods:
- Experiments were conducted using a differentiated neuroblastoma cell line.
- Caffeine was used as a pharmacological activator of ryanodine receptors.
- Ca2+ imaging techniques, including single-cell imaging, were employed.
- Controlled Ca2+ influx through voltage-gated channels was utilized.
Main Results:
- Caffeine released Ca2+ from intracellular stores in a Ca2+-dependent and ryanodine-sensitive manner.
- Cyclic ADP-ribose amplified Ca2+-induced Ca2+ release in a concentration-dependent and ryanodine-sensitive manner.
- Cyclic ADP-ribose increased the sensitivity of intracellular Ca2+ stores to Ca2+ influx and enhanced the spatial spread of Ca2+ signals within the cell.
Conclusions:
- Cyclic ADP-ribose acts as an endogenous modulator of ryanodine receptors in neurons.
- cADPR plays a significant role in amplifying Ca2+ signals initiated by neuronal depolarization and Ca2+ entry.
- These findings suggest cADPR is crucial for coupling neuronal activity to global intracellular Ca2+ signaling.
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