The possible role of phospholipase A2 in cardiac membrane destabilization under calcium overload conditions.
The mechanism of spontaneous diastolic depolarizations induced by different Ca2+ overloading conditions (ouabain toxicity, calcium ionophore A23187, O-K, high Ca2+ solution) in mammalian working myocardium fibres was studied with conventional microelectrode technique and pharmacological approach. Antagonistic properties of antiphospholipase-A2 (PL A2)-active compounds (dexamethasone and indomethacin) were tested. Membrane oscillations in Ca2+ overload conditions were shown to be eliminated or largely protected by both anti-inflammatory agents. There was no influence of the compounds on electrical parameters and ion currents in intact mammalian and amphibian myocardium. The data obtained suggested that modulation of Ca2+-dependent PL A2 activity may contribute significantly to membrane destabilization due to Ca2+ overload of cardiac cells. An analogous membrane destabilizing action of exogenous PL A2 observed in Langendorff-perfused guinea pig heart is in favour of the hypothesis introduced.
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010042:Ouabain / Q000633:toxicity; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011895:Rana ridibunda
D010042:Ouabain; D003907:Dexamethasone; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium; D007213:Indomethacin