# MYOSIN ISOZYMES AND CONTRACTION IN DEVELOPING MUSCLES

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1991 · $164,551

## Abstract

Studies of mammalian skeletal and cardiac   muscles have shown that
the contractile protein myosin undergoes transitions in subunit structure
during development from embryo to adult.  We will investigate the
physiological roles of the isoforms of myosin in rat and rabbit
myocardium and in rabbit skeletal muscles.  This will be done using
single muscle fibers and cardiac myocytes from which the surface
membranes have been removed, allowing direct control of activation with
Ca2+ . Maximum tension, the rate of tension development, stiffness, and
shortening velocity will be measured to determine mechanical properties
of myosin cross-bridges and overall kinetics of the cross-bridge
interaction cycle.  Specific cross-bridge state transitions will be
studied by characterizing isometric tension transients in response to
rapid photorelease of Pi, ADP or the Ca 2+ chelator BAPTA from chemically
caged compounds.  The myosin heavy and light chain compositions of these
same single cells will then be determined using ultrasensitive gel
electrophoretic techniques. (1) These measurements will be made on
cardiac muscle and on fast and slow skeletal muscles at fetal, neonatal
and adult stages of development, as well as on rabbit fast-twitch
skeletal muscles subjected to altered patterns of stimulation in vivo.
(2) Further experiments will directly test the hypothesis that the types
and proportions of myosin light chains modulate contraction.  This will
be done by performing mechanical measurements on single cardiac myocytes
and skeletal muscle fibers both before and after exchanging various
isoforms of the alkali light chains for the endogenous light chains in
these cells. (3) Molecular mechanisms of light chain effects on
mechanical properties will be investigated by substituting truncated or
mutated alkali light chain-1 for endogenous light chains. (4) Mechanical
properties of skinned myocytes from senescent myocardium will be
characterized to determine whether myosin heavy chains expressed in aged
rats account for altered cardiac function in senescence.
     Measurements of contractile properties in single muscle cells as
functions of natural and imposed variations in protein composition should
allow straightforward conclusions regarding physiological roles of
diverse myosin isoforms.  Additional experiments will provide insight
regarding cross-bridge state transitions that are sensitive to altered
expression of myosin and molecular mechanisms of effects due to altered
expression.

## Key facts

- **NIH application ID:** 3156098
- **Project number:** 2R01AR031806-09A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** Richard L Moss
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $164,551
- **Award type:** 2
- **Project period:** 1983-01-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156098

## Citation

> US National Institutes of Health, RePORTER application 3156098, MYOSIN ISOZYMES AND CONTRACTION IN DEVELOPING MUSCLES (2R01AR031806-09A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156098. Licensed CC0.

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