Hystereses in the force-length relation and regulation of cross-bridge recruitment in tetanized rat trabeculae

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 286; no. 1; pp. H434 - H441
• Main Authors: Levy, Carmit, Landesberg, Amir
• Format: Journal Article
• Language: English
• Published: United States 01.01.2004
• Subjects: Animals; Electric Stimulation; In Vitro Techniques; Myocardial Contraction - physiology; Oscillometry; Papillary Muscles - anatomy & histology; Papillary Muscles - physiology; Papillary Muscles - ultrastructure; Rats; Rats, Sprague-Dawley; Sarcomeres - physiology; Sarcomeres - ultrastructure; Time Factors
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00354.2003

Department of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa 32000, Israel Submitted 14 April 2003 ; accepted in final form 8 September 2003 Various mechanisms have been suggested to explain cardiac force-length Ca 2+ relations. The existence of a cooperativity mechanism, whereby cross-bridge (XB) recruitment is affected by the number of active XBs, suggests that the force response to length oscillations should lag length oscillations. Consequently, the oscillatory force response should be larger during shortening than during lengthening. To test this prediction, force responses to large-sarcomere length (SL) oscillations (36.7 ± 16.0 nm) at different SLs ( n = 6) and frequencies ( n = 7) were studied in intact tetanized trabeculae dissected from rat right ventricle ( n = 13). Stable tetani were obtained by utilizing 30 µM cyclopiazonic acid in Krebs-Henseleit solution containing 6 mM extracellular Ca 2+ at 25°C. SL was measured by laser diffraction techniques (Dalsa). Force was measured by silicone strain gauge. Instantaneous dynamic stiffness during large oscillations was measured by superimposing additional fast (50 or 200 Hz) and small-amplitude (2.25 ± 0.25 nm) oscillations. The force responses lagged the SL oscillations at slow frequencies (112 ± 41 ms at 1 Hz), and counterclockwise hystereses were obtained in the force-length plane: the force was higher during shortening than during lengthening. The delay in the force response decreased as the frequency of the SL oscillation was increased. Clockwise hysteresis, where the force preceded the SL, was obtained at frequencies >4 Hz. Similar hysteresis characteristics were obtained in the force-SL and stiffness-SL planes. Maximal lag was observed at the shortest SL, and the delay decreased with sarcomere elongation: 131.1 ± 31.7 ms at 1.78 ± 0.03 µm vs. 14.7 ± 18.5 ms at 1.99 ± 0.015 µm. The results establish the ability of cardiac fiber to adapt XB recruitment to changes in prevailing loading conditions. This study supports the stipulated existence of a cooperativity mechanism that regulates XB recruitment and highlights an additional method to characterize regulation of the force-length relation. excitation-contraction coupling; Frank-Starling law; regulated actin; troponin Address for reprint requests and other correspondence: A. Landesberg, Dept. of Biomedical Engineering, Technion-IIT, Haifa 32000, Israel (E-mail: amir{at}biomed.technion.ac.il ).