Shortening the thick filament by partial deletion of titin's C-zone alters cardiac function by reducing the operating sarcomere length range.

ABSTRACT: Titin's C-zone is an inextensible segment in titin, comprised of 11 super-repeats and located in the cMyBP-C-containing region of the thick filament. Previously we showed that deletion of titin's super-repeats C1 and C2 (Ttn^ΔC1-2 model) results in shorter thick filaments and contractile dysfunction of the left ventricular (LV) chamber but that unexpectedly LV diastolic stiffness is normal. Here we studied the contraction-relaxation kinetics from the time-varying elastance of the LV and intact cardiomyocyte, cellular work loops of intact cardiomyocytes, Ca²⁺ transients, cross-bridge kinetics, and myofilament Ca²⁺ sensitivity. Intact cardiomyocytes of Ttn^ΔC1-2 mice exhibit systolic dysfunction and impaired relaxation. The time-varying elastance at

SUBMITTER: Methawasin M 

PROVIDER: S-EPMC8940690 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature