ArticleBiophysical journal2015
Importance of the Voltage Dependence of Cardiac Na/K ATPase Isozymes.
Article in Biophysical journal, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- On the mechanism of hypomagnesemia with treatment-resistant seizures caused by variants of the Na+,K+-ATPase α1 subunit (ATP1A1).The Journal of general physiology · 2026Article
- The electrogenicity of the NaeLife · 2025Article
- Multistate Kinetic Model of the Sodium-Potassium ATPase.The journal of physical chemistry. B · 2025Article
- Astrocyte Kir4.1 expression level territorially controls excitatory transmission in the brain.Cell reports · 2025Article
- ATP1A1-linked diseases require a malfunctioning protein product from one allele.Biochimica et biophysica acta. Molecular cell research · 2024Article
- A Na pump with reduced stoichiometry is up-regulated by brine shrimp in extreme salinities.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Clarifying the composition of the ATP consumption factors required for maintaining ion homeostasis in mouse rod photoreceptors.Scientific reports · 2023Article
- Resilience of compound action potential peaks to high-frequency firing in the mouse optic nerve.Physiological reports · 2023Article
- Role of a conserved ion-binding site tyrosine in ion selectivity of the Na+/K+ pump.The Journal of general physiology · 2022Article
- How expensive is the astrocyte?Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Role of NaJournal of molecular medicine (Berlin, Germany) · 2022Review
- Regulation of Cardiac Contractility by the Alpha 2 Subunit of the NaFrontiers in physiology · 2022Review
- Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease.The Journal of membrane biology · 2021Article
- Diseases caused by mutations in the NaAmerican journal of physiology. Cell physiology · 2021Review
- Roles of Key Ion Channels and Transport Proteins in Age-Related Hearing Loss.International journal of molecular sciences · 2021Review
- FXYD proteins and sodium pump regulatory mechanisms.The Journal of general physiology · 2021Review
- Loss of the K+ channel Kv2.1 greatly reduces outward dark current and causes ionic dysregulation and degeneration in rod photoreceptors.The Journal of general physiology · 2021Article
- FXYD protein isoforms differentially modulate human Na/K pump function.The Journal of general physiology · 2020Article
- Physiological Effects of the Electrogenic Current Generated by the NaBioelectricity · 2020Article
- Distinct effects of Q925 mutation on intracellular and extracellular NaScientific reports · 2019Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac cells express more than one isoform of the Na, K-ATPase (NKA), the heteromeric enzyme that creates the Na(+) and K(+) gradients across the plasmalemma. Cardiac isozymes contain one catalytic α-subunit isoform (α1, α2, or α3) associated with an auxiliary β-subunit isoform (β1 or β2). Past studies using biochemical approaches have revealed minor kinetic differences between isozymes formed by different α-β isoform combinations; these results make it difficult to understand the physiological requirement for multiple isoforms. In intact cells, however, NKA enzymes operate in a more complex environment, which includes a substantial transmembrane potential. We evaluated the voltage dependence of human cardiac NKA isozymes expressed in Xenopus oocytes, and of native NKA isozymes in rat ventricular myocytes, using normal mammalian physiological concentrations of Na(+)o and K(+)o. We demonstrate that although α1 and α3 pumps are functional at all physiologically relevant voltages, α2β1 pumps and α2β2 pumps are inhibited by ∼75% and ∼95%, respectively, at resting membrane potentials, and only activate appreciably upon depolarization. Furthermore, phospholemman (FXYD1) inhibits pump function without significantly altering the pump's voltage dependence. Our observations provide a simple explanation for the physiological relevance of the α2 subunit (∼20% of total α subunits in rat ventricle): they act as a reserve and are recruited into action for extra pumping during the long-lasting cardiac action potential, where most of the Na(+) entry occurs. This strong voltage dependence of α2 pumps also helps explain how cardiotonic steroids, which block NKA pumps, can be a beneficial treatment for heart failure: by only inhibiting the α2 pumps, they selectively reduce NKA activity during the cardiac action potential, leading to an increase in systolic Ca(2+), due to reduced extrusion through the Na/Ca exchanger, without affecting resting Na(+) and Ca(2+) concentrations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.