Document Detail


Phospholipid lysophosphatidylcholine as a metabolic trigger and HERG as an ionic pathway for extracellular K accumulation and "short QT syndrome" in acute myocardial ischemia.
MedLine Citation:
PMID:  17762169     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The most profound abnormalities during acute myocardial ischemia are extracellular K(+) accumulation ([K(+)](o)- upward arrow) and shortening of action potential duration or QT interval (APD- downward arrow or QT- downward arrow), which are pivotal in the genesis of ischemic arrhythmias and sudden cardiac death. The ionic mechanisms however remained obscured. We performed studies in a rabbit model of acute global myocardial ischemia in order to explore ionic and metabolic mechanisms for ischemic [K(+)](o)- upward arrow and QT- downward arrow. Exogenous 1-palmitoyl-lysophosphatidylcholine (LPC-16) mimicked the low-perfusion ischemia to produce significant [K(+)](o)- upward arrow and QT- downward arrow. The [K(+)](o)- upward arrow and QT- downward arrow induced by either LPC-16 or ischemia were prevented by dofetilide, a blocker of rapid delayed rectifier K(+) current (I(Kr)), but not by blockers for other K(+) channels. Consistently, dofetilide efficiently abolished the ventricular tachy-arrhythmias induced by ischemia or LPC-16. LPC-16 remarkably shortened APD and enhanced the function of I(Kr) and HERG (the pore-forming subunit of I(Kr)). The effects of LPC-16 manifested with shorter APD (faster repolarization rate) and at more negative potential (membrane repolarization). Dofetilide abolished the I(Kr)/HERG enhancing and APD shortening effects of LPC-16. Our results suggest that LPC-16 accumulation/HERG enhancement may be a link between metabolic trigger and ionic pathway for ischemic [K(+)](o)- upward arrow and QTc- downward arrow. This represents the first documentation of I(Kr)/HERG as the ionic mechanism in ischemic [K(+)](o)- upward arrow and QTc- downward arrow. Inhibition of LPC-16 production and accumulation and/or of I(Kr)/HERG may be a promising therapeutic strategy to attenuate the incidence of lethal arrhythmias associated with ischemic heart disease.
Authors:
Yunlong Bai; Jingxiong Wang; Yanjie Lu; Hongli Shan; Baofeng Yang; Zhiguo Wang
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  20     ISSN:  1015-8987     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2007  
Date Detail:
Created Date:  2007-08-31     Completed Date:  2007-09-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  417-28     Citation Subset:  IM    
Copyright Information:
Copyright (c) 2007 S. Karger AG, Basel.
Affiliation:
Department of Pharmacology (State and Provincial Key Laboratory of China), Harbin Medical University, Harbin, Heilongjiang, China.
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MeSH Terms
Descriptor/Qualifier:
Acute Disease
Animals
Cell Line
Guinea Pigs
Humans
Ions / chemistry,  metabolism
Lysophosphatidylcholines / pharmacology*
Myocardial Ischemia / metabolism*
Potassium / metabolism*
Potassium Channel Blockers / pharmacology
Potassium Channels / metabolism
Rabbits
Signal Transduction / drug effects*
Chemical
Reg. No./Substance:
0/Ions; 0/Lysophosphatidylcholines; 0/Potassium Channel Blockers; 0/Potassium Channels; 7440-09-7/Potassium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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