Sarcomere integrated biosensor detects myofilament-activating ligands in real time during twitch contractions in live cardiac muscle.

ABSTRACT: The sarcomere is the functional unit of cardiac muscle, essential for normal heart function. To date, it has not been possible to study, in real time, thin filament-based activation dynamics in live cardiac muscle. We report here results from a cardiac troponin C (TnC) FRET-based biosensor integrated into the cardiac sarcomere via stoichiometric replacement of endogenous TnC. The TnC biosensor provides, for the first time, evidence of multiple thin filament activating ligands, including troponin I interfacing with TnC and cycling myosin, during a cardiac twitch. Results show that the TnC FRET biosensor transient significantly precedes that of peak twitch force. Using small molecules and genetic modifiers known to alter sarcomere activation, independently of the intracellular Ca²⁺

SUBMITTER: Vetter AD 

PROVIDER: S-EPMC7584764 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature