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

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.

Source: Journal of Molecular and Cellular Cardiology - January 10, 2022 Category: Cytology Authors: Mei Methawasin, Gerrie P. Farman, Shawtaroh Granzier-Nakajima, Joshua Strom, Balazs Kiss, John E. Smith, Henk Granzier Source Type: research