# CA2+ REGULATION OF MUSCLE CONTRACTION

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 1992 · $297,691

## Abstract

During the past four years we have made major progress in the
development of several model systems for studying the regulation of
muscle contraction. These include reconstituted thin filaments, TnC
depleted reconstituted skinned fibers and intact muscle fibers. These
systems combined with the techniques of fluorescence spectroscopy, flash
photolysis of caged compounds, time resolved X-ray diffraction and
proteolytic fragments of the regulatory proteins have allowed us to
discover many new features about muscle activation/relaxation. In the
present application, we propose to pursue several major questions
related to these processes and have divided the application into two
major areas of study as follows: I. The use of skinned and intact muscle
fibers to study muscle activation and relaxation processes. The
following specific aims will be pursued: I-1. What are the temporal
relationships between: a) the binding of Ca2+ to the regulatory sites of
TnC (measured by incorporated fluorescent TnC derivatives) and the
activation of force development and stiffness of skinned fiber systems
from rabbit, frog and barnacle muscle following rapid step changes in
free Ca2+ (photolysis of caged Ca2+) which are not limited by diffusion
processes and: b) the dissociation of Ca2+ from the regulatory sites of
TnC and force relaxation and stiffness following rapid step decreases in
free Ca2+ (photolysis of the caged Ca2+ chelator, diazo-2)? I-2. What
are the effects of different crossbridge states (e.g. increment[ATP],
increment [ADP]/[ATP], increment[Pi], rigor (-ATP), weakly attached (N-
phenylmaleimide treated) and numbers (e.g. different sarcomere lengths,
length perturbations) on these processes? I-3. What is the time course
for Ca2+ binding to TnC in intact single muscle fibers, particularly
barnacle, when activated electrically? I-4. During relaxation, what is
the relation between free Ca2+ and the attached crossbridge states? I-5.
Can the rates of force development and force relaxation observed in
electrically excited intact frog, barnacle and scallop (myosin
regulated) fibers be increased by laser flash photolysis of caged
calcium or caged calcium chelator injected directly into the cell? I-6.
What is the Ca2+ affinity of rabbit light chain-2 of myosin in situ and
can it play a role in muscle regulation? II. The use of proteolytic
fragments of Tn and Tm to study muscle regulation. The following
specific aims will be pursued: II-1. What are the roles the different
regions of TnC in the regulation of contraction? II-2. What are the
roles of the head-to-tail interaction of Tm and the NH2-terminal region
of TnT in the cooperative activation of muscle contraction? II-3. What
are the interactions of the different regions of TnI with the other thin
filament proteins and how are these related to the activation and
relaxation of muscle contraction? Taken together these unique approaches
should yield a much clearer view of the temporal and molecular events
involved in...

## Key facts

- **NIH application ID:** 3158292
- **Project number:** 2R01AR037701-06A1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **SAM.gov UEI:** F8THLJQSAF93
- **Principal Investigator:** JAMES Douglas POTTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $297,691
- **Award type:** 2
- **Project period:** 1986-07-01 → 1996-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3158292

## Citation

> US National Institutes of Health, RePORTER application 3158292, CA2+ REGULATION OF MUSCLE CONTRACTION (2R01AR037701-06A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3158292. Licensed CC0.

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