Alexei Verkhratsky1,2, Mohamed Trebak3, Fabiana Perocchi4,5, Daniel Khananshvili6, Israel Sekler7. 1. Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK. 2. Achucarro Center for Neuroscience, IKERBASQUE, Basque Foundation for Science, Bilbao, Spain. 3. Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, USA. 4. Gene Center/Department of Biochemistry, Ludwig-Maximilians Universität München, Munich, Germany. 5. Institute for Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany. 6. Department of Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Ramat-Aviv, Israel. 7. Department of Physiology and Cell Biology, Faculty of Health Science, Ben-Gurion University, Beer-Sheva, Israel.
Abstract
NEW FINDINGS: What is the topic of this review? This paper overviews the links between Ca2+ and Na+ signalling in various types of cells. What advances does it highlight? This paper highlights the general importance of ionic signalling and overviews the molecular mechanisms linking Na+ and Ca2+ dynamics. In particular, the narrative focuses on the molecular physiology of plasmalemmal and mitochondrial Na+ -Ca2+ exchangers and plasmalemmal transient receptor potential channels. Functional consequences of Ca2+ and Na+ signalling for co-ordination of neuronal activity with astroglial homeostatic pathways fundamental for synaptic transmission are discussed. ABSTRACT: Transmembrane ionic gradients, which are an indispensable feature of life, are used for generation of cytosolic ionic signals that regulate a host of cellular functions. Intracellular signalling mediated by Ca2+ and Na+ is tightly linked through several molecular pathways that generate Ca2+ and Na+ fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca2+ release with generation of Na+ and Ca2+ currents. The plasmalemmal Na+ -Ca2+ exchanger (NCX) flickers between forward and reverse mode to co-ordinate the influx and efflux of both ions with membrane polarization and cytosolic ion concentrations. The mitochondrial calcium uniporter channel (MCU) and mitochondrial Na+ -Ca2+ exchanger (NCLX) mediate Ca2+ entry into and release from this organelle and couple cytosolic Ca2+ and Na+ fluctuations with cellular energetics. Cellular Ca2+ and Na+ signalling controls numerous functional responses and, in the CNS, provides for fast regulation of astroglial homeostatic cascades that are crucial for maintenance of synaptic transmission.
NEW FINDINGS: What is the topic of this review? This paper overviews the links between Ca2+ and Na+ signalling in various types of cells. What advances does it highlight? This paper highlights the general importance of ionic signalling and overviews the molecular mechanisms linking Na+ and Ca2+ dynamics. In particular, the narrative focuses on the molecular physiology of plasmalemmal and mitochondrial Na+ -Ca2+ exchangers and plasmalemmal transient receptor potential channels. Functional consequences of Ca2+ and Na+ signalling for co-ordination of neuronal activity with astroglial homeostatic pathways fundamental for synaptic transmission are discussed. ABSTRACT: Transmembrane ionic gradients, which are an indispensable feature of life, are used for generation of cytosolic ionic signals that regulate a host of cellular functions. Intracellular signalling mediated by Ca2+ and Na+ is tightly linked through several molecular pathways that generate Ca2+ and Na+ fluxes and are in turn regulated by both ions. Transient receptor potential (TRP) channels bridge endoplasmic reticulum Ca2+ release with generation of Na+ and Ca2+ currents. The plasmalemmal Na+ -Ca2+ exchanger (NCX) flickers between forward and reverse mode to co-ordinate the influx and efflux of both ions with membrane polarization and cytosolic ion concentrations. The mitochondrial calcium uniporter channel (MCU) and mitochondrial Na+ -Ca2+ exchanger (NCLX) mediate Ca2+ entry into and release from this organelle and couple cytosolic Ca2+ and Na+ fluctuations with cellular energetics. Cellular Ca2+ and Na+ signalling controls numerous functional responses and, in the CNS, provides for fast regulation of astroglial homeostatic cascades that are crucial for maintenance of synaptic transmission.
Authors: Liron Boyman; Brian M Hagen; Moshe Giladi; Reuben Hiller; W Jonathan Lederer; Daniel Khananshvili Journal: J Biol Chem Date: 2011-06-16 Impact factor: 5.157
Authors: Marta Pérez-Hernández; Alejandra Leo-Macias; Sarah Keegan; Mariam Jouni; Joon-Chul Kim; Esperanza Agullo-Pascual; Sarah Vermij; Mingliang Zhang; Feng-Xia Liang; Paul Burridge; David Fenyo; Eli Rothenberg; Mario Delmar Journal: Circ Res Date: 2020-12-21 Impact factor: 17.367