The mechanisms of the Frank-Starling law and familial cardiomyopathy are different. The function of myosin binding protein-C is retained on myocyte length increase and force generated is kinase controlled

Abstract

I have recently reiterated that the cross-bridge is a calcium ATPase that is inhibited by magnesium and this arises because in normal hearts Myosin binding Protein-C prevents the use of MgATP as rate limiting substrate ensuring that Ca 2+ replaces Mg 2+ in the excitation pathway. Here I revisit the studies on [Ca 2+ ] dependency of ATPase and tension under diastolic stretch with a different conclusion on Hill coefficients. This reveals the underlying mechanisms of the Frank-Starling Law and Hypertrophic myopathy are not the same, the former being kinase controlled.

Angiotensin II type 1 receptor and the activation of Myosin Light-Chain Kinase and Protein Kinase C-βII: Mini Review

“…My recent study [5] of the mechanism of FSLH led me to reconsider the Ca 2+ cooperativity of contraction of an unperturbed heart [6] and its inhibition [7] by Mg 2+ . The conclusion of this was that the cross-bridge ATPase is dependent on Ca 2+ binding at two sites.…”

“…The requirement of both the exchange of Ca 2+ for Mg 2+ and the cross-bridge initiation by Ca 2+ binding to troponin-C (Tn-C) [10,11] makes the Ca 2+ activation of the cross-bridge cooperative [5] i.e. the Hill coef icient for Ca 2+ activation is 2.…”

“…As there is no change in the Ca 2+ cooperativity, Hill coef icient, the length induced shift to lower [Ca 2+ ] activation is simply the result of raising the effective Ca 2+ af inity of either the cTn-C or the MgADP-phosphomyosin [5,6,8,9]. A recent study by Zhang, et al [14], with structural sensitive probes indicates that it is changes in the myosin head region, myosin light chain 2 (MLC2), that are responsible for the stretch induced ampli ication of maximal tension.…”