Actions of arachidonic acid on contractions and associated electrical activity in guinea-pig isolated ventricular myocytes

The actions of arachidonic acid (AA) were investigated in guinea-pig isolat ed ventricular myocytes. Exposure of myocytes to 10 mum AA reduced the ampl itude of contractions and calcium transients accompanying action potentials at a frequency of 1 Hz. AA (10 mum) also reduced the amplitude of calcium currents recorded under voltage-clamp conditions. The suppression of contra ction by AA was not prevented by either 10 mum trihydroindomethicin (to inh ibit cyclo-oxygenase) or 10 mum ETYA (5,8,11,14-eicosatetraynoic acid, to i nhibit AA metabolising enzymes), showing that the actions of AA appeared no t to be mediated by these metabolites. The reduction of contraction by Wpm AA was also not prevented by the protein kinase C inhibitor, Ro31-8220 (1 m um), showing that this pathway appeared not to be required for the observed effect. Direct effects of AA may be involved. A further action of 10 mum A A was to suppress spontaneous electrical activity induced by either the bet a -adrenergic agonist isoprenaline or the Na+ pump inhibitor, ouabain. This effect of AA on spontaneous activity might be associated with the observed reduction of calcium entry through L-type calcium channels, although addit ional effects of AA on calcium release from the sarcoplasmic reticulum migh t also be involved.