title: Arachidonic acid disrupts calcium dynamics in neonatal rat cardiac myocytes.
abstract: OBJECTIVE
  The purpose of this study was to investigate the effects of prolonged arachidonic acid (AA) exposure on electrically induced fluctuations of cytosolic free Ca2+ concentration ([Ca2+]i) in cardiac myocytes and to identify intracellular biochemical events that may play a role in the actions of AA on [Ca2+]i dynamics.
  
  
  METHODS
  Electrically induced [Ca2+]i transients were investigated in cultured single neonatal rat ventricular myocytes using spectrofluorometric analysis of fura-2-[Ca2+]i binding. KCl-induced depolarization, caffeine and ryanodine were used to assess the effects of AA on Ca2+ handling by the sarcolemma and the sarcoplasmic reticulum. Prostanoid formation was measured with an ELISA technique. alpha-Tocopherol was used to determine if free radical formation was a factor in the AA effects on [Ca2+]i.
  
  
  RESULTS
  Exposure to 10-30 microM AA produced a concentration-dependent and reversible configuration change and eventually a cessation of [Ca2+]i transients. Continued exposure resulted in a Ca2+ overload (tonic [Ca2+]i greater than peak systolic [Ca2+]i). AA did not influence KCl-induced [Ca2+]i increase but did eliminate caffeine-induced [Ca2+]i transients. AA exposure stimulated the formation of 6-oxo-prostaglandin F1 alpha in a concentration-dependent manner, but thromboxane B2 formation was not influenced. alpha-Tocopherol pretreatment significantly delayed times till cessation of [Ca2+]i transients and Ca2+ overload, whereas ryanodine and cyclo-oxygenase inhibitors were without effect.
  
  
  CONCLUSIONS
  The present data provide evidence that the initial action of AA on [Ca2+]i transients during excitation-contraction coupling involves an effect of AA on sarcolemmal Ca2+ influx and sarcoplasmic reticulum Ca2+ handling. AA-induced cessation of electrically induced [Ca2+]i transients and Ca2+ overload may involve the formation of free radicals.
authors: Center for Disease Control and Prevention, National Institute for Occupational Safety and Health, Cincinnati, OH 45226, USA.
authors: P
authors: P
authors: Hoffmann
authors: D
authors: D
authors: Richards
authors: I
authors: I
authors: Heinroth-Hoffmann
authors: P
authors: P
authors: Mathias
authors: H
authors: H
authors: Wey
authors: M
authors: M
authors: Toraason
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004797:Enzyme-Linked Immunosorbent Assay; D017136:Ion Transport / Q000187:drug effects; D008041:Linoleic Acids / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
chemical_list: D008041:Linoleic Acids; D014810:Vitamin E; D016718:Arachidonic Acid; D002110:Caffeine; D015121:6-Ketoprostaglandin F1 alpha; D011189:Potassium Chloride; D015126:8,11,14-Eicosatrienoic Acid; D002118:Calcium