title: Lysophosphatidylcholine-induced Ca(2+)-overload in isolated cardiomyocytes and effect of cytoprotective drugs.
abstract: It has been previously demonstrated that lysophosphatides accumulate rapidly in ischaemic tissue, and may play a key role in the genesis of ischaemia-reperfusion injury. The present study investigated the effects of exogenously added lysophosphatidylcholine (1-20 microM) on single isolated cardiomyocytes from adult rabbit hearts. Quiescent cells exposed to > or = 8 microM lysophosphatidylcholine dose-dependently displayed irreversible hypercontraction, whereas after 60 min at 3 microM lysophosphatidylcholine, most cells remained rod-shaped (87.2 +/- 2.0%, mean +/- S.E.M.). However, when combined with electrical field stimulation (1 Hz), exposure to 3 microM lysophosphatidylcholine resulted in irreversible hypercontracture of most cells after 60 min: only 27.5 +/- 7.5% of the cells remained rod-shaped. Contracture depended upon the presence of extracellular Ca2+, and coincided with a significant rise in the median intracellular free Ca2+ level from 72.2 to 352.1 nM (P = 0.0001), suggesting intracellular Ca(2+)-overload. Pretreatment with 10(-6) M flunarizine or R 56865 significantly reduced the fraction of damaged cells when exposed to 3 microM lysophosphatidylcholine and electrical stimulation: 78.3 +/- 12.2% and 56.3 +/- 13.1% respectively of the cells remained rod-shaped. No protection was observed when quiescent cells were exposed to 10 microM lysophosphatidylcholine. Cytochemical localization of Ca2+ showed that lysophosphatidylcholine induced a loss of sarcolemma-bound Ca2+ precipitate and an accumulation of Ca2+ clusters in mitochondria of damaged cells in a dose and time dependent way. These results suggest that lysophosphatidylcholine induces functional and structural damage (Ca(2+)-overload) in isolated cardiomyocytes and that this can be prevented by cytoprotective drugs.
authors.affiliation: Department of Physiology, Janssen Research Foundation, Beerse, Belgium.
authors.forename: L
authors.initials: L
authors.lastname: Ver Donck
authors.forename: G
authors.initials: G
authors.lastname: Verellen
authors.forename: H
authors.initials: H
authors.lastname: Geerts
authors.forename: M
authors.initials: M
authors.lastname: Borgers
mesh_terms: D000818:Animals; D052160:Benzothiazoles; D002118:Calcium / Q000378:metabolism*; D005444:Flunarizine / Q000494:pharmacology; D006321:Heart / Q000187:drug effects*; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007424:Intracellular Fluid / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011817:Rabbits; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; D008244:Lysophosphatidylcholines; D010880:Piperidines; D013844:Thiazoles; C054551:R 56865; D005444:Flunarizine; D002118:Calcium