ArticleAmerican journal of physiology. Heart and circulatory physiology2017
Kvβ1.1 (AKR6A8) senses pyridine nucleotide changes in the mouse heart and modulates cardiac electrical activity.
Article in American journal of physiology. Heart and circulatory physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Development and testing of nanoparticles delivery for P7C3 small molecule using injury models.Molecular and cellular biochemistry · 2024Article
- Cardioprotective Effects of 1-(3,6-Dibromo-carbazol-9-yl)-3-Phenylamino-Propan-2-Ol in Diabetic Hearts via Nicotinamide Phosphoribosyltransferase Activation.The Journal of pharmacology and experimental therapeutics · 2022Article
- Review
- NADMolecular and cellular biochemistry · 2022Review
- Deletion of Kvβ2 (AKR6) Attenuates Isoproterenol Induced Cardiac Injury with Links to Solute Carrier Transporter SLC41a3 and Circadian Clock Genes.Metabolites · 2021Article
- Metabolic regulation of endothelial SK channels and human coronary microvascular function.International journal of cardiology · 2020Article
- NADFrontiers in physiology · 2020Review
- Metabolic regulation of Kv channels and cardiac repolarization by Kvβ2 subunits.Journal of molecular and cellular cardiology · 2019Article
- Biochemical and physiological properties of KChemico-biological interactions · 2019Review
- Physiological role of Kvβ2 (AKR6) in murine skeletal muscle growth and regulation.Acta physiologica (Oxford, England) · 2018Article
- Statistical considerations in reporting cardiovascular research.American journal of physiology. Heart and circulatory physiology · 2018Article
- Emerging potential benefits of modulating NADAmerican journal of physiology. Heart and circulatory physiology · 2018Review
- Corticosteroids and aldose reductase inhibitor Epalrestat modulates cardiac action potential via Kvβ1.1 (AKR6A8) subunit of voltage-gated potassium channel.Molecular and cellular biochemistry · 2017Article
- Myriad roles of voltage-activated potassium channel subunit Kvβ1.1 in the heart.American journal of physiology. Heart and circulatory physiology · 2017Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The present study investigates the physiological role of Kvβ1 subunit for sensing pyridine nucleotide (NADH/NAD+) changes in the heart. We used Kvβ1.1 knockout (KO) or wild-type (WT) mice and established that Kvβ1.1 preferentially binds with Kv4.2 and senses the pyridine nucleotide changes in the heart. The cellular action potential duration (APD) obtained from WT cardiomyocytes showed longer APDs with lactate perfusion, which increases intracellular NADH levels, while the APDs remained unaltered in the Kvβ1.1 KO. Ex vivo monophasic action potentials showed a similar response, in which the APDs were prolonged in WT mouse hearts with lactate perfusion; however, the Kvβ1.1 KO mouse hearts did not show APD changes upon lactate perfusion. COS-7 cells coexpressing Kv4.2 and Kvβ1.1 were used for whole cell patch-clamp recordings to evaluate changes caused by NADH (lactate). These data reveal that Kvβ1.1 is required in the mediated inactivation of Kv4.2 currents, when NADH (lactate) levels are increased. In vivo, isoproterenol infusion led to increased NADH in the heart along with QTc prolongation in wild-type mice; regardless of the approach, our data show that Kvβ1.1 recognizes NADH changes and modulates Kv4.2 currents affecting AP and QTc durations. Overall, this study uses multiple levels of investigation, including the heterologous overexpression system, cardiomyocyte, ex vivo, and ECG, and clearly depicts that Kvβ1.1 is an obligatory sensor of NADH/NAD changes in vivo, with a physiological role in the heart.
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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.