# MUSCLE ENERGETICS AND CHEMOMECHANICAL TRANSDUCTION

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 1993 · $190,065

## Abstract

The mechanism by which muscle or any other molecular motor converts
chemical energy (ATP) into mechanical work, force, and shortening
(chemomechanical transduction) will be studied.  Current theories of this
process are based on a four step reaction mechanism in which ATP binds
to and dissociates actomyosin, followed by strong binding of the myosin
products complex to actin and the associated sequential release of Pi and
ADP.  The release of products powers the rotation of the myosin head, the
power stroke, and produces the motive force and sliding of the thick and
thin filaments.  The rate of ATP hydrolysis, the force produced, and the
velocity of shortening are all dependent on the rate constants
controlling the transition between different AM states and the rate
constants themselves are a function of the strain on the crossbridge.
Using transient kinetics in solutions of isolated proteins to study the
rates of steps in dissociating or dissociated proteins, and glycerinated
fibers to examine the rate constant for actomyosin transitions and ATP
hydrolysis, and the recently developed in vitro motility assays, we will
test a number of these ideas.  A major challenge to conventional wisdom
are experiments indicating that the power stroke is much larger than
possible by the rotating crossbridge concept.  The power stroke size will
be estimated by measuring the time course of ATP hydrolysis, shortening,
and stiffness in single shortening glycerinated muscle fibers.  In
comparative studies (using motility assays) the power stroke size
produced by myosins from skeletal and smooth muscles and platelets will
be estimated.  Second, using ATP analogues to produce contractions in
which force, rate of force development, Pi transients, and velocity of
shortening are different, we will determine to what extend these
differences are explicable by measured changes in the rate constants of
the actomyosin reaction mechanism.  These same studies, when applied to
motility assays, will allow determination of the extent to which the
motility assay is a paradigm of muscle contraction.  Attempts will be
made to develop a technique by which the number of strongly attached
crossbridges to a length of moving actin filament can be estimated.  If
successful this would allow evaluation as to what extent stiffness is an
adequate measure of the number of attached crossbridges.  Finally an
attempt will be made to load crossbridges and examine their velocity-pCa
relationship.

## Key facts

- **NIH application ID:** 3155947
- **Project number:** 5R01AR030988-12
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **SAM.gov UEI:** RN64EPNH8JC6
- **Principal Investigator:** EARL E HOMSHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $190,065
- **Award type:** 5
- **Project period:** 1982-05-01 → 1997-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3155947

## Citation

> US National Institutes of Health, RePORTER application 3155947, MUSCLE ENERGETICS AND CHEMOMECHANICAL TRANSDUCTION (5R01AR030988-12). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3155947. Licensed CC0.

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