The degree of activation of cardiac muscle depends on muscle length

Abstract

The Frank-Starling mechanism of the heart 1-3 can be described as the relationship between force and length of cardiac muscle. With the advent of the cross bridge theory of muscle contraction 4,5 and Gordon and collaborator's classical study 6 describing the fitting of this theory to the force-length relationship in skeletal muscle, several investigators started to study this relationship in cardiac muscle.The force-length relation in cardiac muscle is observed in a small variety of sarcomere lengths, between approximately 1.8 µm and 2.3 µm. This region corresponds to the ascending limb of the force-length relation of skeletal-muscle 6 . The force levels of the myocardium vary from zero at 1.8 µm to maximal force values at 2.3 µm. This large variation in force results in a very sleep force-length relation, especially when compared with this relation in skeletal muscle ( fig. 1). To get an idea, when the tension developed by the myocardium at different sarcomere lengths is normalized in relation to its maximal force (F max ) at the point where maximal length (L max ) occurs, the developed tension is approximately 10-15% when the myocardium is measured at 80% L max . Yet in skeletal muscle, normalized force is approximately 80-85% of F max 7 under the same conditions ( fig.1).This difference between skeletal and cardiac muscle shows that the force-length relationship in the myocardium are not a simple function of the degree of superposition of actin and myosin filaments. Because their lengths are similar in both muscles, other factors must be involved in the muscle force-length relationship. During recent years, this difference has been attributed to the dependence of muscle activation on sarcomere length 8 .Muscle activation has been used collectively in the literature to refer to various processes able to initiate muscle contraction, modifying the muscle state from "inactive" to "active". Thus, muscle activation has been associated with the frequency of muscle stimulation or membrane action potentials with intracellular Ca 2+ concentration [Ca 2+ ] i , or the occupation of the protein troponin C (TnC) by Ca 2+ . In this article, the term muscle contraction will be utilized to describe the proportion of TnC associated with Ca 2+ . The association TnC/Ca 2+ represents a fundamental event in muscle contraction; therefore, the sensitivity of TnC to Ca 2+ will be discussed in greater detail. This choice, furthermore, comes from studies shewing that myocardial force changes due to muscle length are unrelated to [Ca 2+ ] i 9,10 . The present article contains a review of studies related to the dependence of force and, more importantly, of the process of myocardial muscle activation on muscle length. In particular, the article intends to investigate mechanisms responsible for the dependence of the sensitivity of filaments to Ca 2+ on muscle length, as proposed in the literature.Dependence of the sensitivity of filaments to Ca 2+ on muscle length -Evidence that the activation of the myocardium is dependent on muscle lengt...

Extensive eccentric contractions in intact cardiac trabeculae: revealing compelling differences in contractile behaviour compared to skeletal muscles

“…This range closely corresponds to the ascending limb of the stress -length relation of skeletal muscle (cf. figure 1b, inset) [2,56]. As demonstrated by previous investigations [2,4,57], the excised rat heart trabeculae featured a monotonically increasing FLR.…”

“…figure 1b, inset) [2,56]. As demonstrated by previous investigations [2,4,57], the excised rat heart trabeculae featured a monotonically increasing FLR. This is in contrast with the typical slope change between the shallow and steep slope regions at the ascending limb of the FLR in striated skeletal muscles [5,56].…”

“…Force-producing mechanisms such as the cross-bridge (XB) and sliding filament theory have proved to be similar in cardiac and skeletal muscle tissues [1,2]. Yet, cardiac and skeletal muscle exhibit different contractile behaviour.…”

“…During systole, the heart muscle contracts concentrically only. The physiological working range is restricted to comparatively short sarcomere lengths (SL) that correspond in skeletal muscle to a working range associated with the ascending limb of the force -length relation (FLR) [2]. In cardiac muscle, the passive FLR is an exponential function originating at SLs of about 1.9 mm [3,4].…”