Extracellular heparin inhibits Ca2+ transients and contraction in mammalian cardiac myocytes

Abstract

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