Document Detail

Electrophysiological Effects of Lysophosphatidylcholine on HL-1 Cardiomyocytes Assessed with a Microelectrode Array System.
MedLine Citation:
PMID:  22777069     Owner:  NLM     Status:  Publisher    
Background: Sudden death due to malignant ventricular arrhythmias is the most important cause of death in acute myocardial infarction. Improved knowledge about the pathophysiology underlying these arrhythmias is essential in the search for new anti-arrhythmic strategies. Lysophosphatidylcholine (LPC), a hydrolysis product of (membrane) phospholipid degradation, is one of the most potent pro-arrhythmic substances that accumulate in the human heart during myocardial ischemia. The aim of this study was to set up and validate an in vitro experimental system for studies on the effects of LPC on electrophysiological parameters in beating cardiomyocytes. Methods and Results: Spontaneously beating HL-1 cardiomyocytes were cultured on multielectrode array microchips for three days for the recording of electrical activities in the form of field potentials (FP). FPs were recorded at baseline and after addition of 2, 4, 8, 12, 16, 20, and 24 µM of LPC to the cell medium (n=9). We found that LPC could induce rapid effects on electrical parameters in the HL-1 cells. The overall half-maximal effective concentration (EC(50)) of LPC was around 12 µM. The beating rate and peak-peak amplitude of FP thus decreased at concentrations ≥ 12 µM and were inversely proportional to increased LPC concentration. The duration of FP was significantly prolonged with LPC above 12 µM and was concentration-dependent. LPC delayed signal propagation, an effect which was mimicked by blocking gap junctions with heptanol and attenuated by pre-treatment with isoprenaline and atropine. Finally, asynchronous activity was induced by LPC at >12 µM. Conclusions: LPC induced prompt and pronounced electrophysiological alterations that may underlie its observed pro-arrhythmic properties. Our in vitro model with HL-1 cells and microelectrode array system may be a useful tool for preclinical studies of electrophysiological effects of various pathophysiological concepts.
Sigfus Gizurarson; Yangzhen Shao; Azra Miljanovic; Truls Råmunddal; Jan Borén; Lennart Bergfeldt; Elmir Omerovic
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-7-10
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  30     ISSN:  1421-9778     ISO Abbreviation:  -     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-7-10     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  477-488     Citation Subset:  -    
Copyright Information:
Copyright © 2012 S. Karger AG, Basel.
Department of Molecular and Clinical Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
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