Rate of tension redevelopment is not modulated by sarcomere length in permeabilized human, murine, and porcine cardiomyocytes

• Published in: American journal of physiology. Regulatory, integrative and comparative physiology integrative and comparative physiology, 2007-07, Vol.293 (1), p.R20-R29
• Main Authors: Edes, Istvan Ferenc, Czuriga, Daniel, Csanyi, Gabor, Chlopicki, Stefan, Recchia, Fabio A, Borbely, Attila, Galajda, Zoltan, Edes, Istvan, van der Velden, Jolanda, Stienen, Ger J. M, Papp, Zoltan
• Format: Article
• Language: English
• Subjects: Adult; Animals; Calcium; Calcium - physiology; Cardiology; Cells; Data Interpretation, Statistical; Female; Heart; Hogs; Humans; In Vitro Techniques; Isometric Contraction; Male; Mice; Middle Aged; Myocardial Contraction - physiology; Myocytes, Cardiac - physiology; Myocytes, Cardiac - ultrastructure; Myofibrils - physiology; Myofibrils - ultrastructure; Rodents; Sarcomeres - physiology; Sarcomeres - ultrastructure; Swine
• ISSN: 0363-6119; 1522-1490
• DOI: 10.1152/ajpregu.00537.2006

1 Division of Clinical Physiology, Institute of Cardiology, University of Debrecen, Medical and Health Science Center, Faculty of Medicine, Debrecen, Hungary; 2 Department of Experimental Pharmacology, Chair of Pharmacology, Jagiellonian University Medical College, Krakow, Poland; 3 Sector of Medicine, Scuola Superiore Sant’ Anna, Pisa, Italy; 4 New York Medical College, Valhalla, New York; and 5 Laboratory for Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands Submitted 27 July 2006 ; accepted in final form 13 November 2006 The increase in Ca 2+ sensitivity of isometric force development along with sarcomere length (SL) is considered as the basis of the Frank-Starling law of the heart, possibly involving the regulation of cross-bridge turnover kinetics. Therefore, the Ca 2+ dependencies of isometric force production and of the cross-bridge-sensitive rate constant of force redevelopment ( k tr ) were determined at different SLs (1.9 and 2.3 µm) in isolated human, murine, and porcine permeabilized cardiomyocytes. k tr was also determined in the presence of 10 mM inorganic phosphate (P i ), which interfered with the force-generating cross-bridge transitions. The increases in Ca 2+ sensitivities of force with SL were very similar in human, murine, and porcine cardiomyocytes ( pCa 50 : 0.11). k tr was higher ( P < 0.05) in mice than in humans or pigs at all Ca 2+ concentrations ([Ca 2+ ]) [maximum k tr ( k tr,max ) at a SL of 1.9 µm and pCa 4.75: 1.33 ± 0.11, 7.44 ± 0.15, and 1.02 ± 0.05 s –1 , in humans, mice, and pigs, respectively] but k tr did not depend on SL in any species. Moreover, when the k tr values for each species were expressed relative to their respective maxima, similar Ca 2+ dependencies were obtained. Ten millimolar P i decreased force to 60–65% and left pCa 50 unaltered in all three species. P i increased k tr,max by a factor of 1.6 in humans and pigs and by a factor of 3 in mice, independent of SL. In conclusion, species differences exert a major influence on k tr , but SL does not appear to modulate the cross-bridge turnover rates in human, murine, and porcine hearts. mouse; pig; heart; skinned muscle; myofilament length-dependent activation; rate of tension redevelopment; calcium Address for reprint requests and other correspondence: Z. Papp, Div. of Clinical Physiology, Inst. of Cardiology, Univ. of Debrecen, Medical and Health Science Center, Faculty of Medicine, PO Box 1, H-4004