Calcium-dependent regulation of the voltage-gated sodium channel hH1: intrinsic and extrinsic sensors use a common molecular switch

Proceedings of the National Academy of Sciences of the United States of America
Vikas N ShahWalter J Chazin

Abstract

The function of the human cardiac voltage-gated sodium channel Na(V)1.5 (hH1) is regulated in part by binding of calcium to an EF hand in the C-terminal cytoplasmic domain. hH1 is also regulated via an extrinsic calcium-sensing pathway mediated by calmodulin (CaM) via binding to an IQ motif immediately adjacent to the EF-hand domain. The intrinsic EF-hand domain is shown here to interact with the IQ motif, which controls calcium affinity. Remarkably, mutation of the IQ residues has only a minor effect on CaM affinity but drastically reduces calcium affinity of the EF-hand domain, whereas the Brugada mutation A1924T significantly reduces CaM affinity but has no effect on calcium affinity of the EF-hand domain. Moreover, the differences in the biochemical effects of the mutations directly correlate with contrasting effects on channel electrophysiology. A comprehensive model is proposed in which the hH1 IQ motif serves as a molecular switch, coupling the intrinsic and extrinsic calcium sensors.

References

Jul 26, 1990·Nature·J Babitch
Aug 24, 1995·Nature·P B BennettA L George
May 19, 1995·The Journal of Biological Chemistry·J C McPheeW A Catterall
Dec 6, 1994·Proceedings of the National Academy of Sciences of the United States of America·J C McPheeW A Catterall
Jan 20, 1999·Biochemistry·C A RohlR E Klevit
Jan 25, 2002·Nature·Hanno L TanJeffrey R Balser
Jun 11, 2002·Analytical Biochemistry·Ingemar André, Sara Linse
Oct 26, 2002·Journal of Biomolecular NMR·Hiroaki IshidaMichio Yazawa
Jul 3, 2003·Journal of Structural and Functional Genomics·K L YapM Ikura
Jul 16, 2003·Biochemical and Biophysical Research Communications·Masayuki MoriKeiji Imoto
Jan 28, 2004·The Journal of General Physiology·Howard K MotoikeRobert S Kass
Feb 26, 2004·Nature Structural & Molecular Biology·Tammy L WingoJeffrey R Balser
Aug 19, 2004·The Journal of Biological Chemistry·James KimGeoffrey S Pitt

❮ Previous
Next ❯

Citations

Jul 25, 2017·The Journal of Physiology·Mena AbdelsayedPeter C Ruben
Feb 14, 2008·The Journal of General Physiology·Subrata BiswasGordon F Tomaselli
Aug 17, 2006·American Journal of Physiology. Renal Physiology·Whaseon Lee-KwonThomas L Pallone
Dec 2, 2006·Cardiovascular Research·Geoffrey S Pitt
Jan 22, 2010·The Journal of Biological Chemistry·Hai M Nguyen, Alan L Goldin
Sep 23, 2011·Cardiovascular Research·Martin B RookMarti F A Bierhuizen
Feb 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Maen F SarhanChristopher A Ahern
Feb 8, 2013·Circulation·Lia CrottiAlfred L George
Apr 23, 2013·The FEBS Journal·Henning Tidow, Poul Nissen
May 30, 2015·Circulation. Arrhythmia and Electrophysiology·Franck PotetAlfred L George
Sep 1, 2014·ESC Heart Failure·Balazs Horvath, Donald M Bers
Oct 1, 2017·The Biochemical Journal·Juan ZouJenny J Yang
Sep 9, 2017·The Journal of Biological Chemistry·Sophie BurelCéline Marionneau
Aug 26, 2018·International Journal of Molecular Sciences·Jianing LiFeng Guo
Jan 9, 2019·Frontiers in Cardiovascular Medicine·Beatrice BadoneAntonio Zaza
Jun 27, 2006·The Journal of Biological Chemistry·Ian W GlaaserRobert S Kass
Nov 9, 2007·Annual Review of Physiology·Donald M Bers
Mar 20, 2012·Nature Communications·Ian W GlaaserRobert S Kass
Jul 2, 2015·The Journal of Physiology·Mena AbdelsayedPeter C Ruben
Feb 2, 2019·The Journal of Physiology·Christopher N Johnson
May 14, 2019·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Eunice Yon June ParkInsuk So
Dec 24, 2018·Frontiers in Cardiovascular Medicine·Maria-Christina KottaLia Crotti
Sep 7, 2006·Pflügers Archiv : European journal of physiology·Juliet A Usher-SmithChristopher L-H Huang
Aug 15, 2013·Scientific Reports·Vishnu Priyanka Reddy ChichiliJ Sivaraman
Mar 7, 2009·Circulation Research·Subrata BiswasGordon F Tomaselli
Jan 1, 2014·Global Cardiology Science & Practice·Thomas ZimmerSteve Blechschmidt
Mar 17, 2015·The Journal of Physiology·Ye Chen-IzuDonald M Bers
Aug 1, 2015·Circulation. Arrhythmia and Electrophysiology·Rui HuaRobert A Rose
Feb 28, 2018·Scientific Reports·Mena AbdelsayedPeter C Ruben
Jan 9, 2009·The Journal of Biological Chemistry·Vesselin Z MiloushevArthur G Palmer
Jan 28, 2009·The Journal of Biological Chemistry·Franck PotetJeffrey R Balser
Apr 24, 2013·Pflügers Archiv : European journal of physiology·Nadezda V KovalevskayaGeerten W Vuister
Jun 5, 2016·Protein Science : a Publication of the Protein Society·Geoffrey S Pitt, Seok-Yong Lee
May 13, 2020·The Korean Journal of Physiology & Pharmacology : Official Journal of the Korean Physiological Society and the Korean Society of Pharmacology·Julia Young BaikInsuk So
Jan 28, 2012·Therapeutic Advances in Gastroenterology·Arthur Beyder, Gianrico Farrugia
Dec 17, 2008·The Journal of Biological Chemistry·Benjamin ChagotWalter J Chazin
Dec 12, 2020·The Journal of General Physiology·Sara NathanL Mario Amzel
Jan 5, 2021·European Journal of Applied Physiology·Michael I Lindinger, Simeon P Cairns

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adhesion Molecules in Health and Disease

Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.

Cardiac Electrophysiology

Cardiac electrophysiology is the study of electrical activities of the heart and includes the assessment, diagnosis, and treatment of cardiac events. Find the latest research on cardiac electrophysiology here.