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Event: 2186
Key Event Title
Ryanodine receptor activation
Short name
Biological Context
| Level of Biological Organization |
|---|
| Molecular |
Cell term
Organ term
| Organ term |
|---|
| brain |
Key Event Components
Key Event Overview
AOPs Including This Key Event
| AOP Name | Role of event in AOP | Point of Contact | Author Status | OECD Status |
|---|---|---|---|---|
| Co-activation of IP3R and RyR to lower IQ | MolecularInitiatingEvent | Karine Audouze (send email) | Under development: Not open for comment. Do not cite |
Taxonomic Applicability
Life Stages
Sex Applicability
| Term | Evidence |
|---|---|
| Unspecific |
Key Event Description
Ryanodine receptor activation refers to the opening of intracellular calcium release channels located primarily on the sarcoplasmic and endoplasmic reticulum membranes.
These receptors, especially RyR1 (in skeletal muscle), RyR2 (in myocardium), and RyR3 (in various tissues including the brain), play a critical role in calcium-induced calcium release (CICR). Activation of these receptors leads to an increased cytosolic calcium concentration, which is essential for numerous physiological processes such as muscle contraction, neuronal signaling, and hormone secretion.
Aberrant or sustained activation can result in dysregulated calcium homeostasis, contributing to pathological conditions like neurotoxicity.
How It Is Measured or Detected
- assessment of calcium release (FRET)
- direct assessment: activation via caffeine, Ca2+, Mg2+
- possibility of confirmation with RyR inhibitors: DHBP
Domain of Applicability
References
- Van Petegem F. (2012). Ryanodine receptors: structure and function. The Journal of biological chemistry, 287(38), 31624–31632. https://doi.org/10.1074/jbc.R112.349068
- Gong, D., Yan, N., & Ledford, H. A. (2021). Structural Basis for the Modulation of Ryanodine Receptors. Trends in biochemical sciences, 46(6), 489–501. https://doi.org/10.1016/j.tibs.2020.11.009