title: Role of reverse mode Na+/Ca2+ exchanger in the cardioprotection of metabolic inhibition preconditioning in rat ventricular myocytes.
abstract: This study determined the role of the reverse mode Na(+)/Ca(2+) exchanger (NCX) in cardioprotection of metabolic inhibition preconditioning in isolated ventricular myocyctes. Activity of the reverse mode NCX was assessed by changes of [Ca(2+)](i) upon withdrawal of extracellular Na(+). [Ca(2+)](i) was measured by spectrofluorometry, using Fura-2 as Ca(2+) indicator. The amplitude of contraction and exclusion of trypan blue by myocytes served as indices of contractile function and viability, respectively. Firstly, NCX activity significantly decreased during simulated reperfusion after severe metabolic inhibition (index ischaemia) in myocytes subjected to metabolic inhibition preconditioning. This inhibitory effect on NCX activity correlated with the enhancing effect of metabolic inhibition preconditioning on cell viability following ischaemic insult. Treatment myocytes with E4031, an activator of reverse mode NCX, during index ischaemia and reperfusion attenuated the enhancing effects of metabolic inhibition preconditioning on cell contraction and viability. Secondly, NCX activity was significantly higher at the end of metabolic inhibition preconditioning. More importantly, E4031 pretreatment mimicked the beneficial effects of metabolic inhibition preconditioning in myocytes and ischaemic preconditioning in the isolated perfused heart, respectively, and these effects were abolished by KB-R7943, an inhibitor of reverse mode NCX. The results indicate that increased reverse mode NCX activity during preconditioning triggered cardioprotection, and reduced reverse mode NCX activity during reperfusion after index ischaemia conferred cardioprotection.
authors.affiliation: Department of Physiology, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Shu-Zhuang
authors.initials: SZ
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Geng-Ze
authors.initials: GZ
authors.lastname: Wei
authors.forename: Zhen-Xiao
authors.initials: ZX
authors.lastname: Jin
authors.forename: Yi-Min
authors.initials: YM
authors.lastname: Zang
authors.forename: Jing-Jun
authors.initials: JJ
authors.lastname: Zhou
authors.forename: Tak-Ming
authors.initials: TM
authors.lastname: Wong
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002470:Cell Survival; D016257:Fura-2 / Q000032:analysis; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000201:enzymology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000502:physiology*; D013050:Spectrometry, Fluorescence; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D016276:Ventricular Function / Q000187:drug effects / Q000502:physiology
chemical_list: C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D011725:Pyridines; D019831:Sodium-Calcium Exchanger; C063968:E 4031; D013890:Thiourea; D002118:Calcium; D016257:Fura-2