EXTRACELLULAR HEPARIN INHIBITS CA2+ TRANSIENTS AND CONTRACTION IN MAMMALIAN CARDIAC MYOCYTES

The effect of heparin on Ca2+ transients and cell shortening was studi ed in isolated cardiac myocytes from rat and guinea-pig ventricles. Ca 2+ signals were measured with the fluorescent indicator fura-2. Hepari n reversibly decreased Ca2+ transients and cell shortening in a dose-d ependent manner. Half and complete blockade were obtained with 50 mu g /ml and 200 mu g/ml heparin, respectively. The dihydropyridine agonist BAY K 8644 (50 nM) antagonized the effects of heparin. However, Ca2release elicited by caffeine (10 mM) was not affected by heparin. The actions of heparin were also studied in multicellular preparations. In papillary muscle, heparin (5 mg/ml) reversibly reduced the amplitude of the plateau of the action potential and the associated peak tension . BAY K 8644 (500 nM) also antagonized these effects. It is proposed t hat heparin interacts with dihydropyridine-sensitive Ca2+ channels to cause a decrease of Ca2+ transients and contractility in heart.