Ranolazine decreases mechanosensitivity of the voltage-gated sodium ion channel Na(v)1.5: a novel mechanism of drug action.

Circulation
Arthur BeyderGianrico Farrugia

Abstract

Na(V)1.5 is a mechanosensitive voltage-gated sodium-selective ion channel responsible for the depolarizing current and maintenance of the action potential plateau in the heart. Ranolazine is a Na(V)1.5 antagonist with antianginal and antiarrhythmic properties. Mechanosensitivity of Na(V)1.5 was tested in voltage-clamped whole cells and cell-attached patches by bath flow and patch pressure, respectively. In whole cells, bath flow increased peak inward current in both murine ventricular cardiac myocytes (24±8%) and human embryonic kidney 293 cells heterologously expressing Na(V)1.5 (18±3%). The flow-induced increases in peak current were blocked by ranolazine. In cell-attached patches from cardiac myocytes and Na(V)1.5-expressing human embryonic kidney 293 cells, negative pressure increased Na(V) peak currents by 27±18% and 18±4% and hyperpolarized voltage dependence of activation by -11 mV and -10 mV, respectively. In human embryonic kidney 293 cells, negative pressure also increased the window current (250%) and increased late open channel events (250%). Ranolazine decreased pressure-induced shift in the voltage dependence (IC(50) 54 μmol/L) and eliminated the pressure-induced increases in window current and late current event ...Continue Reading

References

Jan 25, 1992·Proceedings of the National Academy of Sciences of the United States of America·M E GellensR G Kallen
Aug 10, 1995·The New England Journal of Medicine·B J MaronF O Mueller
Aug 24, 1995·Nature·P B BennettA L George
Jun 1, 1997·Journal of Molecular and Cellular Cardiology·H Hu, F Sachs
Dec 21, 2000·American Journal of Physiology. Heart and Circulatory Physiology·G R Li, C M Baumgarten
Aug 24, 2002·Circulation Research·Margaret P ChandlerHani N Sabbah
Oct 25, 2002·Pflügers Archiv : European journal of physiology·Stephen R BeschFrederick Sachs
Nov 14, 2002·The Journal of Biological Chemistry·Yijun OuGianrico Farrugia
Dec 12, 2002·American Journal of Physiology. Cell Physiology·Peter R StregeGianrico Farrugia
Apr 19, 2003·The EMBO Journal·Denice M HodgsonAndre Terzic
May 7, 2003·Progress in Biophysics and Molecular Biology·Ursula Ravens
Aug 2, 2003·American Journal of Physiology. Gastrointestinal and Liver Physiology·Peter R StregeGianrico Farrugia
Dec 8, 2004·Proceedings of the National Academy of Sciences of the United States of America·Peter J MohlerVann Bennett
Apr 30, 2005·Current Opinion in Cardiology·Peter J Mohler, Vann Bennett
Mar 8, 2006·British Journal of Pharmacology·Sandra FredjRobert S Kass
Apr 28, 2006·Clinical Pharmacokinetics·Markus Jerling
Jun 3, 2006·Methods in Molecular Biology·Catherine E MorrisUlrike Laitko
Oct 10, 2006·Journal of Molecular and Cellular Cardiology·Heather FraserAlexander S Clanachan
May 15, 2007·Biophysical Journal·Catherine E Morris, Peter F Juranka
Apr 15, 2008·The Journal of Biological Chemistry·Amelia MazzoneGianrico Farrugia
Jul 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Kazuo UedaJonathan C Makielski
Jul 5, 2008·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Serge SicouriCharles Antzelevitch
Dec 4, 2008·Proceedings of the National Academy of Sciences of the United States of America·Daniel Schmidt, Roderick MacKinnon
Sep 12, 2009·Journal of Molecular and Cellular Cardiology·Hugues Abriel
Nov 3, 2009·Heart Rhythm : the Official Journal of the Heart Rhythm Society·Sridharan RajamaniLuiz Belardinelli
Dec 4, 2009·The Journal of Biological Chemistry·Elisa RedaelliEnzo Wanke
Jan 22, 2010·Channels·Umberto BanderaliCatherine E Morris
Nov 3, 2010·The Journal of Physiology·Arthur BeyderGianrico Farrugia
Jun 11, 2011·Frontiers in Physiology·Catherine E Morris

❮ Previous
Next ❯

Citations

Jul 7, 2012·Current Heart Failure Reports·Lars S Maier
Dec 25, 2012·Future Cardiology·Jordi HeijmanDobromir Dobrev
Feb 18, 2014·Pflügers Archiv : European journal of physiology·Byambajav BuyandelgerRalph Knöll
May 27, 2014·Naunyn-Schmiedeberg's Archives of Pharmacology·Stefan DheinFriedrich-Wilhelm Mohr
Oct 26, 2014·Cardiovascular Research·Teddy GrandStephan Rohr
Sep 21, 2013·Current Cardiology Reports·Kapil Kumar, Peter J Zimetbaum
Nov 8, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Christos G MihosOrlando Santana
Dec 18, 2015·Seminars in Cell & Developmental Biology·Alejandra Leo-MaciasMario Delmar
Jan 21, 2016·Nature Communications·Alejandra Leo-MaciasMario Delmar
Nov 18, 2015·The Journal of General Physiology·Radda RusinovaOlaf S Andersen
Jun 5, 2016·Cardiac Electrophysiology Clinics·Mohammad ShenasaHossein Shenasa
Mar 19, 2013·Journal of Molecular and Cellular Cardiology·Lars S Maier, Samuel Sossalla
Dec 25, 2012·Journal of Molecular and Cellular Cardiology·Natalia Shirokova, Ernst Niggli
Aug 10, 2012·Channels·Arthur BeyderGianrico Farrugia
Jul 1, 2014·Progress in Biophysics and Molecular Biology·T Alexander QuinnUrsula Ravens
Jul 31, 2012·Progress in Biophysics and Molecular Biology·Rachel M A ter Bekke, Paul G A Volders
Apr 27, 2016·Scientific Reports·Jan KubanekJianmin Cui
Jul 29, 2016·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Chen WangQiang Tang
Jan 7, 2018·The Journal of Biological Chemistry·Samrat Roy, M K Mathew
Nov 24, 2017·American Journal of Physiology. Gastrointestinal and Liver Physiology·Peter R StregeGianrico Farrugia
Feb 28, 2014·Clinical Medicine Insights. Therapeutics·Mohammed AldakkakAmadou K S Camara
Jul 3, 2013·The Journal of Pharmacology and Experimental Therapeutics·Giorgio Minotti
Jul 18, 2015·American Journal of Physiology. Gastrointestinal and Liver Physiology·Leila NeshatianGianrico Farrugia
Jul 14, 2017·Archives of Pharmacal Research·Joon-Chul KimSun-Hee Woo
Nov 16, 2019·Pflügers Archiv : European journal of physiology·Michele MaroniEsther Eberhardt
May 7, 2020·Frontiers in Pharmacology·Balázs HorváthTamás Bányász
Dec 8, 2017·Herzschrittmachertherapie & Elektrophysiologie·Jordi Heijman, Dobromir Dobrev
Sep 1, 2014·ESC Heart Failure·Balazs Horvath, Donald M Bers
Jan 31, 2019·Frontiers in Endocrinology·Arthur Beyder
Aug 28, 2020·Frontiers in Physiology·Irene Del-CantoAndreu M Climent
Dec 2, 2020·Channels·Kornél KistamásPéter P Nánási
Jan 11, 2018·Biophysical Journal·Frederick Sachs
Aug 8, 2021·International Journal of Molecular Sciences·Maximilian TrumStefan Wagner

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antiarrhythmic Agents: Mechanisms of Action

Understanding the mechanism of action of antiarrhythmic agents is essential in developing new medications as treatment of cardiac arrhythmias is currently limited by the reduced availability of safe and effective drugs. Discover the latest research on Antiarrhythmic Agents: Mechanism of Action here.

Cardiology Journals

Discover the latest cardiology research in this collection of the top cardiology journals.

Anti-Arrhythmic Drug Therapies

Anti-arrhythmic drugs are used to prevent abnormal heart rhythms. These medications are used in conditions including, ventricular tachycardia, ventricular fibrillation and atrial fibrillation. Discover the latest research on anti-arrhythmic drug therapies here.

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Antianginal Drugs: Mechanisms of Action

Antianginal drugs, including nitrates, beta-blockers, and calcium channel blockers, are used in the treatment of angina pectoris. Here is the latest research on their use and their mechanism of action.