# ANALYSIS OF CELLULAR CALCIUM COMPARTMENTS IN MUSCLE

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 1993 · $118,322

## Abstract

The contractile system of vertebrate skeletal and cardiac muscle is
activated by the binding of calcium to troponin C. Considerable information
is available on the relationship between free Ca2+ concentration and
mechanical response in skinned fiber preparations, as well as on the
biochemical properties of the regulatory proteins (troponin C, troponin I,
troponin T, tropomyosin) which mediate Ca2+ activation. Less is known about
the relationship between bound Ca2+ and mechanical response in the intact
myofilament system. Recent investigations have shown that not only is
contraction activated by binding of Ca2+ to troponin C but the properties
of troponin C are influenced by the mechanical state of the muscle. This is
best illustrated by recent studies in this laboratory and elsewhere showing
that the steep relationship between contractile force and sarcomere length
in cardiac muscle (Frank-Starling relation) is largely determined by a
length dependence of Ca2+-troponin C affinity. The goal of this research
will be to define the cooperative interactions between contractile and
regulatory proteins which determine the Ca2+ binding properties of troponin
C in the intact myofilament system and determine where these interactions
differ in skeletal and cardiac muscle. A combination of mechanical
measurements, isotopic Ca2+ binding, and fluorescence spectroscopy will be
used to address the following questions: 1) What are the contributions of
cross-bridge interactions and length-dependent Ca2+ binding to the shapes
of the ascending limb of the force-length curves in skeletal and cardiac
muscle? 2) Are apparent length dependent changes in Ca2+ sensitivity or
Ca2+ binding based on changes in length per se, cross-bridge attachments,
or interfilament spacing? 3) What are the quantitative differences between
skeletal and cardiac troponin C with respect to cooperative effects of
cross-bridge interaction and shortening? 4) In interactions between
adjacent troponin units play a role in cross-bridge mediated changes in the
Ca2+-troponin C interaction, and 5) What structural changes take place in
cardiac troponin C in association with Ca2+ binding and cross-bridge
interactions?

## Key facts

- **NIH application ID:** 3154717
- **Project number:** 5R01AR010551-28
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **SAM.gov UEI:** MKAGLD59JRL1
- **Principal Investigator:** FRANKLIN FUCHS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $118,322
- **Award type:** 5
- **Project period:** 1978-05-01 → 1995-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3154717

## Citation

> US National Institutes of Health, RePORTER application 3154717, ANALYSIS OF CELLULAR CALCIUM COMPARTMENTS IN MUSCLE (5R01AR010551-28). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3154717. Licensed CC0.

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