Abstract for Paper VI

The Frank–Starling Law of the Heart; The coupling of stretch to substrate change: A Review

Recent studies have demonstrated that control of cardiac muscle contraction is via two distinct Ca²⁺ binding sites. These sites are the binding site on troponin-C and a considerably lower affinity site that is both ATP activated and Mg²⁺ inhibited. Binding of Ca²⁺ to these sites is responsible for activation of the thin-filament and thick-filament respectively and the experimental isolation of these has been shown along with their contributions to the Hill coefficient of Ca²⁺ activation. The Frank–Starling Law, increased contraction as a result of stretch in diastole, is readily explained as resulting from a stretch-induced negation of the requirement for Ca²⁺ to replace Mg²⁺ in activation of the thick-filament. All the filaments in the contractile active C-region of the sarcomere have a high degree of 3-dimensional organization. The multiple contact at each point on both the thick- and thin-filaments, in both resting and active state, implies double headed myosin contact with multiple actin filaments. This paper reviews the position to date regarding how the change in substrate for cross bridge recruitment may be brought about by the change in length of the sarcomere in diastole.