title: Alterations in Ca2+ cycling by lysoplasmenylcholine in adult rabbit ventricular myocytes.
abstract: We previously reported that lysoplasmenylcholine (LPlasC) altered the action potential (AP) and induced afterdepolarizations in rabbit ventricular myocytes. In this study, we investigated how LPlasC alters excitation-contraction coupling using edge-motion detection, fura-PE3 fluorescent indicator, and perforated and whole cell patch-clamp techniques. LPlasC increased contraction, myofilament Ca(2+) sensitivity, systolic and diastolic free Ca(2+) levels, and the magnitude of Ca(2+) transients concomitant with increases in the maximum rates of shortening and relaxation of contraction and the rising and declining phases of Ca(2+) transients. In some cells, LPlasC induced arrhythmias in a pattern consistent with early and delayed aftercontractions. LPlasC also augmented the caffeine-induced Ca(2+) transient with a reduction in the decay rate. Furthermore, LPlasC enhanced L-type Ca(2+) channel current (I(Ca,L)) and outward currents. LPlasC-induced alterations in contraction and I(Ca,L) were paralleled by its effect on the AP. Thus these results suggest that LPlasC elicits distinct, potent positive inotropic, lusitropic, and arrhythmogenic effects, resulting from increases in Ca(2+) influx, Ca(2+) sensitivity, sarcoplasmic reticular (SR) Ca(2+) release and uptake, SR Ca(2+) content, and probably reduction in sarcolemmal Na(+)/Ca(2+) exchange.
authors.affiliation: Department of Pharmaceutical Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA. sliu@uams.edu
authors.forename: Shi J
authors.initials: SJ
authors.lastname: Liu
authors.forename: Richard H
authors.initials: RH
authors.lastname: Kennedy
authors.forename: Michael H
authors.initials: MH
authors.lastname: Creer
authors.forename: Jane
authors.initials: J
authors.lastname: McHowat
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D004553:Electric Conductivity; D016257:Fura-2 / Q000031:analogs & derivatives*; D006352:Heart Ventricles; D006706:Homeostasis / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011817:Rabbits; D016276:Ventricular Function / Q000187:drug effects
chemical_list: D020746:Calcium Channels, L-Type; D008246:Lysophospholipids; C098106:fura-PE3; C021215:lysoplasmalogens; D002118:Calcium; D016257:Fura-2