This Event is licensed under the Creative Commons BY-SA license. This license allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. If you remix, adapt, or build upon the material, you must license the modified material under identical terms.

Event: 1562

Key Event Title

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

Decreased Na/K ATPase activity

Short name

The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help

Explore in a Third Party Tool

Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help

Level of Biological Organization
Cellular

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

Process	Object	Action
sodium:potassium-exchanging ATPase activity	sodium:potassium-exchanging ATPase complex	decreased

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
Complex I inhibition leads to Fanconi syndrome	KeyEvent	Marvin Martens (send email)	Under development: Not open for comment. Do not cite
Uncoupling of OXPHOS leading to growth inhibition 4	KeyEvent	You Song (send email)	Under development: Not open for comment. Do not cite	Under Development
Na+ /K+ -ATPase inhibition leading to hypertension	MolecularInitiatingEvent	Michelle Angrish (send email)	Under development: Not open for comment. Do not cite
Decreased Na/K ATPase activity leads to Heart failure	MolecularInitiatingEvent	John Frisch (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

Term	Scientific Term	Evidence	Link
Animals	Metazoa	High	NCBI

Life Stages

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

Life stage	Evidence
All life stages	High

Sex Applicability

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

Term	Evidence
Unspecific	High

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

The sodium/potassium (Na/K) ATPase is an active pump that consumes ATP to transport 3 sodium ions (Na + ) out of the cell against its electrochemical gradient, in exchange for 2 potassium ions (K + ). A decrease in Na/K activity can come from a decrease in ATP available to perform this reaction or direct blocking of the pump.

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

Na/K ATPase activity can be measured in cell lysates preserving enzymatic activity, and corresponds to the difference between total ATPase activity and ouabain-sensitive ATPase activity. The measurement can use the leftover ATP or inorganic phosphate produced during ATP hydrolysis as its primary substrate, followed by coupling to colorimetric or fluorimetric dye (Baginski, Foa, and Zak 1967; Nowak 2002) (NovusBio kit 601-0120). Generally Na/K ATPase activity is measured via immunoblots or spectrophotometry; historically electrophysiology measurements of charge changes was more common (Moyes et al. 2021).

Domain of Applicability

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

Life Stage: Applies to all life stages; not specific to any life stage.

Sex: Applies to both males and females; not sex-specific.

Taxonomic: Present broadly in animals as evolutionarily conserved across taxa.

References

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

Baginski, E. S., P. P. Foa, and B. Zak. 1967. “Determination of Phosphate: Study of Labile Organic Phosphate Interference.” Clinica Chimica Acta 15(1):155–58. Retrieved December 6, 2017

Moyes, C.D. Dastjerdi, S.H., Robertson, R.M. 2021. Measuring enzyme activities in crude homogenates: Na+/K+-ATPase as a case study in optimizing assays. Comparative Biochemistry and Physiology, Part B 255: 110577.

Nowak, Grazyna. 2002. “Protein Kinase C-Alpha and ERK1/2 Mediate Mitochondrial Dysfunction, Decreases in Active Na+ Transport, and Cisplatin-Induced Apoptosis in Renal Cells.” The Journal of Biological Chemistry 277(45):43377–88. Retrieved December 5, 2017 (http://www.ncbi.nlm.nih.gov/pubmed/12218054).

NOTE: Italics symbolize edits from John Frisch