© 2000 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Calpain-I induced alterations in the cytoskeletal structure and impaired mechanical properties of single myocytes of rat heart
aDepartment of Physiology, University Medical School of Debrecen, H-4012 Debrecen, Hungary
bInstitute for Cardiovascular Research, Laboratory for Physiology, Vrije Universiteit (ICaR-VU), Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands
* Corresponding author. Tel.: +36-52-416-634; fax: +36-52-432-289 pz{at}phys.dote.hu
Objective: The involvement of Calpain-I mediated proteolysis has been implicated in myofibrillar dysfunction of reperfused myocardium following ischemia (stunning). This study addresses the question whether ultrastructural alterations might be responsible for the depressed contractility. Methods: Mechanical properties and protein composition of isolated myocytes after Calpain-I exposure (1.25 U/ml; 10 min; 15°C; pCa 5.0) and of ischemic rat hearts following reperfusion were characterized. Results: Maximal isometric force (44±5 kN/m2) at pCa 4.5 (pCa=–log[Ca2+]) decreased by 42.5% in Triton permeabilized myocytes (n=11) after Calpain-I treatment. Force (and consequent myofilament disarrangement) during Calpain-I treatment was prevented by 40 mM BDM. The contractile force of Calpain-I exposed myocytes was significantly higher at submaximal levels of activation (pCa 5.5, 5.4 and 5.3) before maximal force development (pCa 4.5) than after maximal force development. The pCa50 value (5.40±0.02) determined from these initial test contractures did not differ significantly from that of untreated controls (5.44±0.03). However, after full activation Ca2+-sensitivity of force production in Calpain-I treated myocytes was significantly reduced (pCa50 5.34±0.02). This change in pCa50 was positively correlated with the reduction in maximal isometric force and was accompanied by sarcomere disorder. These findings imply that at least part of the Calpain-I induced mechanical alterations are dependent on force history. Measurements of the rate of force redevelopment after unloaded shortening suggested that Calpain-I did not affect cross-bridge kinetics. SDS gel electrophoresis and Western immunoblotting of Calpain-I treated myocytes revealed desmin degradation. The desmin content of postischemic myocardium was also reduced. Conclusion: Our results indicate that ultrastructural alterations may play an important role in the Calpain-I mediated cardiac dysfunction.
KEYWORDS Contractile apparatus; Contractile function; Myocytes; Stunning
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