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Event: 2037

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Inositol triphosphate receptor activation

Short name

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Activation, IP3R

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Biological Context

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Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place. For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable. For individual/population events, the organ context is not applicable. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling). The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor). Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description. To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons. If a desired term does not exist, a new term request may be made via Term Requests. Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add. Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help

AOP Name	Role of event in AOP	Point of Contact	Author Status	OECD Status
Calcium overload driven development of parkinsonian motor deficits	MolecularInitiatingEvent	Julia Meerman (send email)	Under development: Not open for comment. Do not cite
Co-activation of IP3R and RyR to lower IQ and socio-economic burden	MolecularInitiatingEvent	Karine Audouze (send email)	Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Inositol 1,4,5-trisphosphate receptors (IP₃Rs) are intracellular calcium release channels located primarily on the membrane of the endoplasmic reticulum (ER).

There are three major isoforms of IP₃R in mammals:

IP₃R-1: Predominantly expressed in neurons
IP₃R-2: Found in various tissues in glial cells
IP₃R-3: Widespread but particularly abundant in epithelial and exocrine tissues

Upon binding of IP₃ to its receptor (IP3R), the channel undergoes a conformational change that opens the pore, allowing Ca²⁺ stored in the ER lumen to flow into the cytosol. In addition to IP₃, the receptor activation requires Ca²⁺ at nanomolar concentrations, whereas Ca²⁺ at higher concentrations is inhibitory, causing the receptor to be tightly regulated by Ca²⁺.This rise in intracellular calcium concentration triggers a broad range of downstream effects, including:

Gene transcription
Secretion of hormones and neurotransmitters
Cell motility
Synaptic plasticity
Apoptosis under sustained or excessive activation

Dysregulation of IP3R activity is implicated in numerous diseases, including:

Neurodegeneration
Cancer
Liver and cardiac dysfunction
Immune disorders

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

The activation of IP3R can be modulated by various factors:

Sensitization by Ca²⁺
ATP

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided). More help

References

List of the literature that was cited for this KE description. More help

Schmitz, E. A., Takahashi, H., & Karakas, E. (2022). Structural basis for activation and gating of IP₃receptors. Nature communications, 13(1), 1408. https://doi.org/10.1038/s41467-022-29073-2
Rezuchova, I., Hudecova, S., Soltysova, A., Matuskova, M., Durinikova, E., Chovancova, B., Zuzcak, M., Cihova, M., Burikova, M., Penesova, A., Lencesova, L., Breza, J., & Krizanova, O. (2019). Type 3 inositol 1,4,5-trisphosphate receptor has antiapoptotic and proliferative role in cancer cells. Cell death & disease, 10(3), 186. https://doi.org/10.1038/s41419-019-1433-4