Modulation of Ca2+ cycling in cardiac myocytes by arachidonic acid.
It is believed that inotropic agents exert their effects in cardiac muscle via a modulation of Ca2+ cycling; however, the involvement of phospholipase activation and the biochemical pathways participating in inotropic responsiveness remain unclear. The aim of the current study was to determine whether arachidonic acid and/or eicosanoids participate in inotropic responses by modulating Ca2+ cycling in cardiac myocytes. Experiments were performed with populations of freshly isolated, fura-2-loaded adult rat ventricular myocytes. Arachidonic acid stimulated a transient increase in cytosolic free Ca2+, which was still present after addition of EGTA but was significantly reduced by pretreatment with caffeine. Addition of arachidonic acid to either electrically stimulated or quiescent myocytes enhanced the amplitude of the ATP-induced Ca2+ transient. This effect was still observed in the presence of inhibitors of cyclooxygenase, lipoxygenase, and epoxygenase pathways but was significantly diminished after pretreatment with inhibitors of protein kinase C. In contrast, arachidonic acid attenuated the amplitude of electrically induced Ca2+ transients. This effect was mimicked by eicosatetraynoic acid and by the K+ channel agonist pinacidil. The inhibitory effect of eicosatetraynoic acid and arachidonic acid was reversed by addition of fatty acid-free bovine serum albumin. Together, these results suggest that arachidonic acid may play a physiological role in cardiac muscle excitation-contraction coupling as a modulator of sarcolemmal ion channels and/or Ca2+ release from the sarcoplasmic reticulum.
Damron
D S
DS
Department of Cardiovascular Biology, Cleveland Clinic Foundation, OH 44195-5069.
Bond
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D005453:Fluorescence; D016257:Fura-2 / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D016718:Arachidonic Acid; D011189:Potassium Chloride; D000255:Adenosine Triphosphate; D007545:Isoproterenol; D002118:Calcium; D016257:Fura-2