Response of cardiac myocytes to a ramp increase of diacylglycerol generated by photolysis of a novel caged diacylglycerol

Biophysical Journal
X HuangJ W Walker

Abstract

To test the responsiveness of living cells to the intracellular messenger diacylglycerol, we developed a prototype caged diacylglycerol compound, 3-O-(alpha-carboxyl-2,4-dinitrobenzyl)-1 ,2-dioctanoyl-rac-glycerol (designated alpha-carboxyl caged diC(8)), that produces dioctanoylglycerol (diC(8)) on photolysis. Alpha-Carboxyl caged diC(8) is biologically inert toward diacylglycerol kinase and protein kinase C in vitro and is readily incorporated into cardiac myocyte membranes, where it has no effect before irradiation. Exposure to near-UV light releases biologically active diC8 in good yield (quantum efficiency = 0.2). Here we examine a cellular response to controlled elevation of diC8 within single cardiac myocytes. Twitch amplitude was monitored in electrically stimulated myocytes, and a ramp increase in the concentration of diC(8) was generated by continuous irradiation of cells loaded with the caged compound. The myocyte response was biphasic with a positive inotropic phase (39% increase in twitch amplitude), followed by a large negative inotropic phase (>80% decrease). The time to peak inotropy for both phases depended on the light intensity, decreasing from 376 +/- 51 S to 44 +/- 5 s (positive phase) and 422 +/- 118 S to ...Continue Reading

Citations

Dec 1, 2001·Pharmacology & Therapeutics·Y ShigeriN Yumoto
Apr 10, 2014·Biochimica Et Biophysica Acta·Doris HöglingerCarsten Schultz
Apr 22, 2010·Immunology·Morgan Huse
Apr 23, 2008·Current Protocols in Neuroscience·Joseph P Y Kao
Jul 1, 1997·Circulation Research·Y PiJ W Walker
Jun 21, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Seth L RobiaJeffery W Walker
Feb 12, 2017·F1000Research·James Cook, Jay Radke
Mar 11, 2008·American Journal of Physiology. Heart and Circulatory Physiology·Ka Young ChungJeffery W Walker
Dec 22, 2015·Nature Communications·André NadlerCarsten Schultz
Mar 3, 2007·Molecular Pharmacology·Ka Young Chung, Jeffery W Walker
May 28, 2005·Anesthesia and Analgesia·Lawrence A TurnerWai-Meng Kwok
Jul 19, 2000·American Journal of Physiology. Heart and Circulatory Physiology·Y Pi, J W Walker
Nov 19, 2011·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Haishen YangPengfei Wang
Jan 13, 2012·Chembiochem : a European Journal of Chemical Biology·Wataru NomuraHirokazu Tamamura
May 31, 2013·Angewandte Chemie·André NadlerCarsten Schultz
Sep 16, 2003·The Journal of Biological Chemistry·Valentin G RobuJeffery W Walker
Mar 25, 2004·Journal of Cell Science·Xupei Huang, Jeffery W Walker

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antihypertensive Agents: Mechanisms of Action

Antihypertensive drugs are used to treat hypertension (high blood pressure) which aims to prevent the complications of high blood pressure, such as stroke and myocardial infarction. Discover the latest research on antihypertensive drugs and their mechanism of action here.