Extracellular heparin inhibits Ca2+ transients and contraction in mammalian cardiac myocytes.
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.
Garcia
M C
MC
Department of Pharmacology, School of Medicine and Dentistry, University of Rochester, Rochester, NY 14642, USA.
Sanchez
J A
JA
Sharma
V K
VK
Sheu
S S
SS
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism*; D004095:Dihydropyridines / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D016257:Fura-2; D006025:Glycosaminoglycans / Q000494:pharmacology; D006168:Guinea Pigs; D006493:Heparin / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism*; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D004095:Dihydropyridines; D006025:Glycosaminoglycans; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D006493:Heparin; D002118:Calcium; D016257:Fura-2