Increased Ca2+ Sensitivity and Length Dependent Activation in a Mouse Model with Increased Titin-Based Stiffness

Abstract

Length-dependent activation (LDA), the increase in Ca2+ sensitivity that occurs when sarcomere length (SL) is increased, is considered the cellular basis of the Frank-Starling law of the heart. Recent findings suggest that titin-based passive tension is a factor in LDA, and the aim of our study was to test this hypothesis in a mouse model in which the N2B spring element has been excised (N2B KO) and that therefore develops elevated passive tension. Fiber bundles of skinned papillary muscle from left ventricular of N2B KO and WT mice (eight per genotype) were isolated for mechanical tests.