# PHYSIOLOGY AND MYOSIN ISOZYMES OF SKELETAL MUSCLE FIBERS

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 1991 · $183,284

## Abstract

The first goal of this project is to establish the physiological
significance of myosin polymorphism in mammalian skeletal muscle.  The
basic hypothesis to be tested is that each myosin isozyme has unique
force-velocity and energetic properties.  Rather than generalizing the
properties of fast-twitch or slow-twitch mammalian fibers, this project
seeks to establish the quantitative contractile and biochemical
differences among subpopulations of fast- and slow-twitch fibers, and
even among subpopulations of fibers that have been nominally lumped into
the same histochemical type.  The second goal of the project is to begin
to dissect the functions of the myosin subunits.  The project will be
able to separate functional contributions of myosin light chains vs
myosin heavy chains by creating altered combinations of heavy and light
chains within permeabilized muscle fibers.  This project will also
involve the construction of a number of light chain mutants, which will
be expressed in bacteria and reconstituted into permeabilized fibers.
The scope of the investigations will include (1) properties of
permeabilized rabbit fiber segments with their naturally occurring
complement of contractile proteins; (2) permeabilized fibers in which
exchange of the myosin light chains with either naturally occurring
light chains or bacterially synthesized mutant light chains has been
performed; and (3) purified myosin isozymes assessed in an in vitro
assay.  Contractile and biochemical measurements will include force per
cross-sectional area, force-velocity relationship, pCca-force
relationship, isometric actomyosin ATPase activity, the rate of
isometric redevelopment of force and cross-bridge kinetics determined
using "caged" ATP.  This project seeks to uncover the significance of
the range of myosin isozyme distributions found in mammalian skeletal
muscle, and to delineate the functional contributions of each of the
myosin subunits.  The problem takes on greater significance when one
considers that the isozyme composition of skeletal muscle is not
necessarily static.  Mammalian skeletal muscle cells show
activity-dependent changes in expression of the various contractile
proteins isoforms as well as levels of metabolic enzymes.  Plasticity is
relevant not only to normal adaptation to altered activity but also to
adaptation that occurs in neuromuscular disease states.

## Key facts

- **NIH application ID:** 3157322
- **Project number:** 2R01AR035661-04A1
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **SAM.gov UEI:** GM1XX56LEP58
- **Principal Investigator:** H Lee Sweeney
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $183,284
- **Award type:** 2
- **Project period:** 1986-07-01 → 1995-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3157322

## Citation

> US National Institutes of Health, RePORTER application 3157322, PHYSIOLOGY AND MYOSIN ISOZYMES OF SKELETAL MUSCLE FIBERS (2R01AR035661-04A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3157322. Licensed CC0.

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