Cardiac Titin

Phosphorylation of Titin Modulates Passive Stiffness of Cardiac Muscle in a Titin Isoform-dependent Manner

We investigated the effect of protein kinase A (PKA) on passive force in skinned cardiac tissues that express different isoforms of titin, i.e., stiff (N2B) and more compliant (N2BA) titins, at different levels. We used rat ventricular (RV), bovine left ventricular (BLV), and bovine left atrial (BLA) muscles (passive force: RV > BLV > BLA, with the ratio of N2B to N2BA titin, approximately 90:1...

Phosphorylation of titin modulates pas- sive stiffness of cardiac muscle in a titin

Question: How does phosphorylation of titan affect cardiac function? Background: Sarcomeres are the repeating contractile subunits from which the myofibrils of striated muscle are built. Titin is a large sarcomeric protein involved in muscle elasticity and myofibril scaffolding, which provides passive tension to muscle based on physiological demands. In mammalian cardiac tissue, there are two i...

Modulation of titin-based stiffness by disulfide bonding in the cardiac titin N2-B unique sequence.

The giant protein titin is responsible for the elasticity of nonactivated muscle sarcomeres. Titin-based passive stiffness in myocardium is modulated by titin-isoform switching and protein-kinase (PK)A- or PKG-dependent titin phosphorylation. Additional modulatory effects on titin stiffness may arise from disulfide bonding under oxidant stress, as many immunoglobulin-like (Ig-)domains in titin'...

Biochemical and mechanical investigation of cardiac titin isoforms

Phosphoregulation of the Titin-cap Protein Telethonin in Cardiac Myocytes*

Telethonin (also known as titin-cap or t-cap) is a muscle-specific protein whose mutation is associated with cardiac and skeletal myopathies through unknown mechanisms. Our previous work identified cardiac telethonin as an interaction partner for the protein kinase D catalytic domain. In this study, kinase assays used in conjunction with MS and site-directed mutagenesis confirmed telethonin as ...