Review
Biochemistry & Molecular Biology
Ayako Takeuchi, Satoshi Matsuoka
Summary: The gene SLC24A6/SLC8B1 has been identified as the responsible gene for mitochondrial Na+-Ca2+ exchange for over 10 years, leading to a deeper understanding of the structure-function relationships and physiological/pathophysiological contributions of NCLX. Recent achievements regarding NCLX, focusing on its heart-specific characteristics, biophysical properties, spatial distribution in cardiomyocytes, and roles in cardiac functions under physiological and pathophysiological conditions, have been summarized in this review.
Article
Biology
Lise M. Sjogaard-Frich, Andreas Prestel, Emilie S. Pedersen, Marc Severin, Kristian Kolby Kristensen, Johan G. Olsen, Birthe B. Kragelund, Stine Falsig Pedersen
Summary: Through various biophysical techniques, this study reveals the complex interaction mechanism between CaM and NHE1, identifying multiple states and structures of the NHE1:CaM complex that can be modulated by stoichiometries, calcium concentrations, and phosphorylation. Experimental results suggest that CaM may enhance NHE1 regulation and indicate that this structural diversity is relevant to other CaM complexes as well.
Article
Cell Biology
P. Brancaccio, S. Anzilotti, O. Cuomo, A. Vinciguerra, M. Campanile, A. Herchuelz, S. Amoroso, L. Annunziato, G. Pignataro
Summary: Researchers are studying endogenous neuroprotective strategies to identify alternative interventions for neonatal hypoxic-ischemic encephalopathy. They found that hypoxic preconditioning can promote neurogenesis and provide neuroprotection by regulating ionic homeostasis.
CELL DEATH DISCOVERY
(2022)
Article
Cardiac & Cardiovascular Systems
Sathya Velmurugan, Ting Liu, Kuey C. Chen, Florin Despa, Brian O'Rourke, Sanda Despa
Summary: Mitochondrial dysfunction plays a role in cardiac remodeling in type 2 diabetes. This study investigated the effects of type 2 diabetes on mitochondrial calcium fluxes and the subsequent consequences on myocyte function. The results showed that type 2 diabetes reduces mitochondrial calcium concentration, leading to oxidative stress, calcium leak, and mitochondrial dysfunction. Inhibition of the mitochondrial sodium/calcium exchanger can alleviate calcium leak and arrhythmias in type 2 diabetes hearts.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Article
Biochemistry & Molecular Biology
Pi-Cheng Cheng, Ruo-Ciao Cheng, Rong-Chi Huang
Summary: Glutamate induces Ca2+ signaling in the suprachiasmatic nucleus (SCN) by activating intracellular mechanisms involving Na+ loads, Na+/K+-ATPase (NKA), and Na+/Ca2+-exchanger (NCX). The presence of Na+ loads leads to slower Ca2+ clearance and increased rebound Ca2+ suppression. However, even in the absence of external Na+, additional Ca2+ handlers are involved in the slower Ca2+ clearance induced by glutamate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Philipp Hegner, Marzena Drzymalski, Alexander Biedermann, Bernadette Memmel, Melanie Durczok, Michael Wester, Bernhard Floerchinger, Zdenek Provaznik, Christof Schmid, York Zausig, Lars S. Maier, Stefan Wagner
Summary: The novel selective NCX-inhibitor SAR296968 inhibits atrial pro-arrhythmic activity and improves diastolic and contractile function in human atrial myocardium, which may have therapeutic implications, especially for treatment of HFpEF.
Article
Physiology
Alexander M. Clifford, Martin Tresguerres, Greg G. Goss, Chris M. Wood
Summary: During exposure to acidic water, zebrafish utilize a novel mechanism of Na+ uptake that relies on the outwardly directed K+ gradient as a counter-substrate for Na+ and is sensitive to tetraethylammonium (TEA).
Article
Biochemistry & Molecular Biology
Simon Thibault, Valerie Long, Celine Fiset
Summary: Male sex is a significant risk factor for atrial fibrillation (AF), with a higher incidence in men. This study demonstrates major sex differences in intracellular Ca2+ homeostasis in mouse atrial myocytes, including larger Ca2+ transients, enhanced Na+-Ca2+ exchanger (NCX1) function and expression, and more frequent spontaneous Ca2+ releases in males. These differences may contribute to the higher susceptibility of males to AF.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Noor Nadhim Al-Saigh, Shtaywy Abdalla
Summary: This study found that safranal induces vasodilation through the inhibition of calcium influx from extracellular space through L-type Ca2+ channels and the inhibition of Na+/Ca2+ exchanger.
Article
Endocrinology & Metabolism
Han Feng, Hao Shen, Matthew J. Robeson, Yue-Han Wu, Hong-Kun Wu, Geng-Jia Chen, Shuo Zhang, Peng Xie, Li Jin, Yanyun He, Yingfan Wang, Fengxiang Lv, Xinli Hu, Yan Zhang, Rui-Ping Xiao
Summary: The E3 ligase-dead mutant MG53-C14A, a variant of the mitsugumin 53 (MG53) protein, not only protects the heart from acute myocardial injury but also counteracts metabolic stress, making it a potentially important treatment for acute myocardial injury in metabolic disorders, including diabetes and obesity.
Article
Biochemistry & Molecular Biology
Gen L. Takei, Yuhei Ogura, Yoshihiro Ujihara, Fubito Toyama, Keitaro Hayashi, Tomoe Fujita
Summary: Previous studies have shown that extracellular Na+ suppresses hamster sperm hyperactivation by reducing intracellular Ca2+ levels, and this suppressive effect can be canceled by specific inhibitors of Na+/Ca2+-exchanger (NCX). However, direct evidence of the presence and functionality of NCX in hamster spermatozoa is lacking. This study demonstrates the presence of functional NCX1 in hamster spermatozoa and its downregulation upon capacitation to trigger hyperactivation, providing novel insights into the regulation of sperm hyperactivation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Immunology
Jose R. Lopez, Nancy Linares, Jose A. Adams, Alfredo Mijares
Summary: Chagas disease is a leading cause of death and morbidity in Latin America, and this study reveals that chronic elevation of diastolic Ca2+ concentration is associated with the disease. The role of Na+/Ca2+ exchanger (NCX) in this process is also explored, suggesting that inhibitors of NCX may be a potential therapeutic approach for Chagas cardiomyopathy.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biology
Jungmi Choi, Naoki Matoba, Daiki Setoyama, Daiki Watanabe, Yuichiro Ohnishi, Ryuto Yasui, Yuichirou Kitai, Aki Oomachi, Yutaro Kotobuki, Yoichi Nishiya, Michael Paul Pieper, Hiromi Imamura, Motoko Yanagita, Masamichi Yamamoto
Summary: The SGLT2 inhibitor, Empagliflozin, increases mitochondrial ATP levels in a mouse model of diabetes, leading to cardioprotective effects. Empagliflozin, an inhibitor of sodium-glucose co-transporter 2, has been shown to reduce cardiovascular events in patients with type 2 diabetes and established cardiovascular disease. The mechanism behind these effects is still unclear.
COMMUNICATIONS BIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Zikai Liu, Qing Cheng, Xiaoli Ma, Mingke Song
Summary: Pharmacological modulation of the Na+/Ca2+ exchanger (NCX) can suppress melanoma cells and induce cell death, making NCX a potential drug target for cancer therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Natalia F. Oshiyama, Ana H. M. Pereira, Alisson C. Cardoso, Kleber G. Franchini, Jose W. M. Bassani, Rosana A. Bassani
Summary: Recent studies have highlighted significant differences between neonatal and adult cardiomyocytes in terms of intracellular Na+ concentration, Na+ channel density, and voltage-dependence. In neonatal ventricles, Na+ channel activation and inactivation curves shift to the right, making channels more available at diastolic E-m but requiring greater depolarization for excitation. Additionally, neonatal myocytes exhibit higher I-Na density, faster inactivation, and current peak at a less negative transmembrane potential compared to adults.
JOURNAL OF PHYSIOLOGY-LONDON
(2022)