# CA RELEASE FROM SARCOPLASMIC RETICULUM: THE FROG PACKAGE

> **NIH NIH R01** · UNIVERSITY OF TEXAS MED BR GALVESTON · 1989 · $123,423

## Abstract

The objective of the proposed research is to identify which of several
different mechanisms of calcium release from the sarcoplasmic reticulum
(SR) contribute to excitation-contraction coupling in vertebrate skeletal
muscle.  A mechanistic approach will be utilized involving the use of
pharmacologic agents as tools.  Identified pharmacologic agents will be
introduced into muscle fibers in order to test which mechanisms for Ca2+
release are physiologically important.  These determinations will utilize
skeletal muscle fibers voltage clamped in a triple Vaseline gap chamber.
The experiments will involve optical determinations of contractile
thresholds and myoplasmic Ca2+ transients measured using metallochromic
indicator dyes.

The choice of agents used for the muscle fiber studies will be made on the
basis of their effects on different mechanisms of calcium release from
isolated SR.  Specific inhibitors will be identified for SR calcium release
induced by Ca2+, alkalinization, SR depolarization, inositol 1,4,5
triphosphate, quinine and other agents.  These experiments will involve
measurements of Ca 2+ flux across isolated SR membrane vesicles using
spectrophotometric and isotope methods.

The health relatedness of the project is not only pertinent to malignant
hyperthermia (linked to an abnormality in Ca2+ release from SR during
anesthesia) but also more generally to numerous diseases of muscle
weakness.  The results of this investigation will additionally have health
related implications for the cardiovascular and gastrointestinal systems,
where cardiac and smooth muscle rely on Ca2+ release from SR for proper
function.  The results of this investigation may lead to suggestions for
new drug therapies for cardiovascular disease.

## Key facts

- **NIH application ID:** 3156816
- **Project number:** 2R01AR034377-04A2
- **Recipient organization:** UNIVERSITY OF TEXAS MED BR GALVESTON
- **SAM.gov UEI:** MSPWVMXXMN76
- **Principal Investigator:** PHILIP T. PALADE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1989
- **Award amount:** $123,423
- **Award type:** 2
- **Project period:** 1988-04-01 → 1992-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156816

## Citation

> US National Institutes of Health, RePORTER application 3156816, CA RELEASE FROM SARCOPLASMIC RETICULUM: THE FROG PACKAGE (2R01AR034377-04A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3156816. Licensed CC0.

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