Biophysical Society Thematic Meeting | Canterbury 2023

Towards a More Perfect Union: Multi-Scale Models of Muscle and Their Experimental Validation

Monday Speaker Abstracts

MYOSIN BASED REGULATION: THE PLOT THICKENS Thomas C Irving 1 ; 1 Illinois Institute of Technology, Biology, Chicago, IL, USA

There is a growing appreciation that thick filament-based regulation mechanisms act in parallel to the textbook thin filament regulation in striated muscle. Evidence suggesting this comes primarily from 1) biochemical assays showing that, under relaxed conditions, myosin is found either in a disordered-relaxed (DRX) state that are readily for contraction or in a very low ATP consumption, super-relaxed (SRX) state that is unavailable for actin binding and 2) structural assays showing that, in a resting muscle, a large percentage of myosin heads are found in a quasi-helically ordered OFF state held close to the thick filament backbone where this helical ordering is lost when myosin heads are turned ON to participate in contraction. It is widely assumed that myosin heads in the biochemically-defined SRX state are strictly equivalent to the structurally-defined OFF state and heads in the DRX state are strictly equivalent to ON state heads so that SRX and the OFF state can be been used interchangeably. This view now appears to be an over-simplification. Here I discuss the results of small angle X-ray diffraction and ATP turnover studies with various inotropic interventions and tool compounds that demonstrate conditions where SRX/DRX transitions are well correlated with the structural OFF-ON transitions but, importantly, multiple situations where this correlation breaks down. I suggest that the biochemically defined term SRX should be reserved to refer to only the very low ATP consumption state that may or may not be ordered. The structurally defined OFF state should be reserved only to refer to quasi-helically ordered heads closely associated with the thick filament backbone that may or may not be in the SRX. There may also be multiple populations of disordered (DRX) and ordered heads that may or may not be available to interact with actin.

SINGLE MOLECULE IMAGING APPROACHES TOWARDS UNDERSTANDING DUAL FILAMENT REGULATION IN MUSCLE Neil Kad University of Kent, United Kingdom No Abstract

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