Article
Genetics & Heredity
Juilee Rege, Sascha Bandulik, Kazutaka Nanba, Carla Kosmann, Amy R. Blinder, Allein Plain, Pankaj Vats, Chandan Kumar-Sinha, Antonio M. Lerario, Tobias Else, Yuto Yamazaki, Fumitoshi Satoh, Hironobu Sasano, Thomas J. Giordano, Tracy Ann Williams, Martin Reincke, Adina F. Turcu, Aaron M. Udager, Richard Warth, William E. Rainey
Summary: This study identified mutations in the SLC30A1 gene associated with PA. The mutations are located near the zinc-binding site in the coding region of SLC30A1 and may cause abnormal ion transport. PA cases with SLC30A1 mutations showed male dominance and increased levels of aldosterone and 18-oxocortisol.
Article
Multidisciplinary Sciences
Edith Le Floch, Teresa Cosentino, Casper K. Larsen, Felix Beuschlein, Martin Reincke, Laurence Amar, Gian-Paolo Rossi, Kelly De Sousa, Stephanie Baron, Sophie Chantalat, Benjamin Saintpierre, Livia Lenzini, Arthur Frouin, Isabelle Giscos-Douriez, Matthis Ferey, Alaa B. Abdellatif, Tchao Meatchi, Jean-Philippe Empana, Xavier Jouven, Christian Gieger, Melanie Waldenberger, Annette Peters, Daniele Cusi, Erika Salvi, Pierre Meneton, Mathilde Touvier, Melanie Deschasaux, Nathalie Druesne-Pecollo, Sheerazed Boulkroun, Fabio L. Fernandes-Rosa, Jean-Francois Deleuze, Xavier Jeunemaitre, Maria-Christina Zennaro
Summary: This study conducted a genome-wide association study in hypertensive patients and identified three main loci associated with primary aldosteronism. Candidate genes located within these loci were expressed in the adrenal glands and were found to suppress aldosterone production, revealing new mechanisms of disease development.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Wei Chen, Lei Wang, Pengfei Liang, Jason Mast, Clausell Mathis, Catherine Y. Liu, Jin Wei, Jie Zhang, Liying Fu, Luis A. Juncos, Jacentha Buggs, Ruisheng Liu
Summary: This study demonstrates the potential therapeutic effect of using a synchronization modulation electric field to activate Na/K pumps and maintain cellular functions during renal ischemia-reperfusion injury.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Satoko Miyatake, Mitsuhiro Kato, Takuma Kumamoto, Tomonori Hirose, Eriko Koshimizu, Takaaki Matsui, Hideyuki Takeuchi, Hiroshi Doi, Keisuke Hamada, Mitsuko Nakashima, Kazunori Sasaki, Akio Yamashita, Atsushi Takata, Kohei Hamanaka, Mai Satoh, Takabumi Miyama, Yuri Sonoda, Momoko Sasazuki, Hiroyuki Torisu, Toshiro Hara, Yasunari Sakai, Yushi Noguchi, Mazumi Miura, Yoko Nishimura, Kazuyuki Nakamura, Hideyuki Asai, Nodoka Hinokuma, Fuyuki Miya, Tatsuhiko Tsunoda, Masami Togawa, Yukihiro Ikeda, Nobusuke Kimura, Kaoru Amemiya, Asako Horino, Masataka Fukuoka, Hiroko Ikeda, Goni Merhav, Nina Ekhilevitch, Masaki Miura, Takeshi Mizuguchi, Noriko Miyake, Atsushi Suzuki, Shouichi Ohga, Hirotomo Saitsu, Hidehisa Takahashi, Fumiaki Tanaka, Kazuhiro Ogata, Chiaki Ohtaka-Maruyama, Naomichi Matsumoto
Summary: The study identified de novo ATP1A3 variants causing a severe form of polymicrogyria with epilepsy and developmental delay, distinct from traditional clinical features of AHC, RDP, or CAPOS. This suggests a previously unidentified category of polymicrogyria associated with ATP1A3 abnormalities.
Article
Biochemistry & Molecular Biology
Grigori Y. Rychkov, Zeeshan Shaukat, Chiao Xin Lim, Rashid Hussain, Ben J. Roberts, Claudia M. Bonardi, Guido Rubboli, Brandon F. Meaney, Robyn Whitney, Rikke S. Moller, Michael G. Ricos, Leanne M. Dibbens
Summary: The effects of various KCNT1 mutations on the severity of neurological disorders were investigated, and a positive correlation was found between the severity of the disorder and the KCNT1 channel open probability at resting membrane potential. This suggests that gain of function KCNT1 mutations cause epilepsy by increasing resting potassium conductance.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Ryuta Kanai, Flemming Cornelius, Bente Vilsen, Chikashi Toyoshima
Summary: Cryo-electron microscopy was used to study the structure of Na+, K+-ATPase and its variations. The results showed that different reaction states exhibited different biochemical characteristics, and the presence of Mg2+ ions in the transmembrane cation binding sites played a crucial role in the reactions. The binding mechanism of the new-generation cardiotonic steroids (CTSs) did not significantly affect the structure of NKA, and the phospholipid molecules were better resolved in the electron microscopy maps compared to X-ray structures.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Multidisciplinary Sciences
Ryuta Kanai, Flemming Cornelius, Haruo Ogawa, Kanna Motoyama, Bente Vilsen, Chikashi Toyoshima
Summary: The sodium pump (Na+, K+-ATPase, NKA) is crucial for maintaining ion gradients across cell membranes, with cardiotonic steroids (CTSs) acting as specific inhibitors. Different structural features of CTSs result in diverse inhibitory properties, with crystal structures providing insights into their mechanism of action and potential for isoform specific targeting.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Biochemistry & Molecular Biology
Santiago E. Faraj, Wanda M. Valsecchi, Mariela Ferreira-Gomes, Mercedes Centeno, Elina Malen Saint Martin, Natalya U. Fedosova, Juan Pablo FC. Rossi, Monica R. Montes, Rolando C. Rossi
Summary: The Na+/K+-ATPase is a plasma membrane glycoprotein that exchanges intracellular Na+ for extracellular K+ by hydrolyzing ATP. The asymmetric distribution of Na+ and K+ is essential for cellular life. Current research indicates that Na+ becomes spontaneously occluded in the E1 dephosphorylated form of the Na+/K+-ATPase, showing positive interactions between binding sites. Adding ATP does not increase Na+ occlusion.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Wenfei Bo, Rong Che, Qiang Liu, Xiaobo Zhang, Yintao Hou, Yubin Gong
Summary: Terahertz science and technology has promising applications in artificial intelligence. This study investigates the behaviors of Na+, K+-ATPase and energy consumption during terahertz unipolar stimulation. The results show that Na+, K+-ATPases can be activated and remain active for a while before closing after stimulation. The power dissipation is low, indicating the potential for investigations of information communication mechanisms in cells under terahertz stimulation.
Article
Biology
Dylan J. Meyer, Carlos Manlio Diaz-Garcia, Nidhi Nathwani, Mahia Rahman, Gary Yellen
Summary: The activation of neuronal glycolysis is mainly a response to an increase in Na+/K+ pump activity, which is strongly potentiated by the influx of Na+ through the Na+/Ca2+ exchanger during the extrusion of Ca2+.
Article
Anesthesiology
Clemens Reiffurth, Nikolaus Berndt, Adrian Gonzalez Lopez, Karl Schoknecht, Richard Kovacs, Mathilde Maechler, Mirja Grote Lambers, Jens P. Dreier, Alon Friedman, Claudia Spies, Agustin Liotta
Summary: Deep isoflurane anesthesia disrupts cortical ion homeostasis and impairs Na+/K+-ATPase function. Isoflurane increases extracellular potassium and decreases extracellular sodium concentrations. It also leads to a decrease in extracellular calcium levels in the absence of synaptic activity and potassium channel antagonists. Isoflurane slows potassium clearance and impairs Na+/K+-ATPase activity, which could contribute to neuronal dysfunction after deep anesthesia.
Article
Medicine, Research & Experimental
Eva Lausberg, Sebastian Giesselmann, Joseph P. Dewulf, Elsa Wiame, Anja Holz, Ramona Salvarinova, Clara D. van Karnebeek, Patricia Klemm, Kim Ohl, Michael Mull, Till Braunschweig, Joachim Weis, Clemens J. Sommer, Stephanie Demuth, Claudia Haase, Claudia Stollbrink-Peschgens, Francois-Guillaume Debray, Cecile Libioulle, Daniela Choukair, Prasad T. Oommen, Arndt Borkhardt, Harald Surowy, Dagmar Wieczorek, Norbert Wagner, Robert Meyer, Thomas Eggermann, Matthias Begemann, Emile Van Schaftingen, Martin Hausler, Klaus Tenbrock, Lambert van den Heuvel, Miriam Elbracht, Ingo Kurth, Florian Kraft
Summary: Our study reveals that C2orf69 is associated with brain abnormalities, liver dysfunction, and recurrent autoinflammation, as well as influencing mitochondrial function and glycogen metabolism.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Endocrinology & Metabolism
Krishnadev Pillai, Ahmed Fares, Soha Dargham, Jassim Al Suwaidi, Amin Jayyousi, Charbel Abi Khalil
Summary: Primary hyperaldosteronism (PA) is a common cause of hypertension, particularly in patients with diabetes. This study evaluated the cardiovascular impact of PA in patients with established hypertension and diabetes, and found that PA patients had a higher risk of mortality, ischemic stroke, hemorrhagic stroke, acute renal failure, atrial fibrillation, and acute heart failure.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Christian Staehr, Palle Duun Rohde, Nikolaj Thure Krarup, Steffen Ringgaard, Christoffer Laustsen, Jacob Johnsen, Rikke Nielsen, Hans Christian Beck, Jens Preben Morth, Karin Lykke-Hartmann, Nichlas Riise Jespersen, Denis Abramochkin, Mette Nyegaard, Hans Erik Botker, Christian Aalkjaer, Vladimir Matchkov
Summary: The study suggests that mutations in the ATP1A2 gene may lead to disturbed cardiac metabolism and reduced cardiac function, potentially mediated through Na,K-ATPase-dependent reactive oxygen species signaling.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Review
Cell Biology
Kelath Murali Manoj, Daniel A. A. Gideon, Nikolai M. M. Bazhin, Hirohisa Tamagawa, Vijay Nirusimhan, Mahendra Kavdia, Laurent Jaeken
Summary: The redox metabolic paradigm emphasizes the importance of diffusible reactive species (DRS), particularly oxygen-centric radicals, in physiology. This article focuses on the membrane protein Na,K-ATPase (NKA) and its role in neuro-cardio-musculo electrophysiology. Through analyzing diffusion, NKA's structural features, ion transport mechanisms, and inhibitory effects of various substances, a minimalist murburn model is proposed to explain the physiological inhibitory effects of different substances on cells.
JOURNAL OF CELLULAR PHYSIOLOGY
(2023)
Article
Physiology
Dylan J. Meyer, Craig Gatto, Pablo Artigas
JOURNAL OF GENERAL PHYSIOLOGY
(2017)
Article
Multidisciplinary Sciences
Hang N. Nielsen, Kerri Spontarelli, Rikke Holm, Jens Peter Andersen, Anja P. Einholm, Pablo Artigas, Bente Vilsen
SCIENTIFIC REPORTS
(2019)
Article
Physiology
Dylan J. Meyer, Sharan Bijlani, Marilina de Sautu, Kerri Spontarelli, Victoria C. Young, Craig Gatto, Pablo Artigas
JOURNAL OF GENERAL PHYSIOLOGY
(2020)
Review
Physiology
John Q. Yap, Jaroslava Seflova, Ryan Sweazey, Pablo Artigas, Seth L. Robia
Summary: The FXYD proteins are crucial regulatory factors that modulate NKA activity by interacting with it. Recent advances in research have expanded our understanding of the role of FXYD proteins in physiological processes, including their structure, function, and potential implications.
JOURNAL OF GENERAL PHYSIOLOGY
(2021)
Article
Multidisciplinary Sciences
Victoria C. Young, Pablo Artigas
Summary: Utilizing state-specific engineered-disulfide cross-linking, it was demonstrated that the transmembrane segment 2 (M2) of the Na+/K+ pump moves in directions inconsistent with distances observed in existing crystal structures of the pump. This movement was characterized using voltage-clamp fluorometry in single-cysteine mutants, revealing state-dependent fluorescence changes upon labeling with tetramethylrhodamine-6-maleimide (TMRM).
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Physiology
Kerri Spontarelli, Daniel T. Infield, Hang N. Nielsen, Rikke Holm, Victoria C. Young, Jason D. Galpin, Christopher A. Ahern, Bente Vilsen, Pablo Artigas
Summary: The study reveals that a residue Y780 stabilizes the sodium-exclusive ion-binding site of the sodium pump through a hydrogen bond and indirectly controls the interaction of potassium at other ion-binding sites. This finding provides important insights into the mechanism by which the sodium pump distinguishes between sodium and potassium.
JOURNAL OF GENERAL PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Victoria C. Young, Hanayo Nakanishi, Dylan J. Meyer, Tomohiro Nishizawa, Atsunori Oshima, Pablo Artigas, Kazuhiro Abe
Summary: This study investigates ion transport mechanisms by introducing mutations to convert an electroneutral proton/potassium pump into a prototypical electrogenic sodium/potassium pump, explaining their selectivity and phosphorylation mechanisms.
NATURE COMMUNICATIONS
(2022)