# CALCIUM MOVEMENTS IN EXCITATION-CONTRACTION COUPLING

> **NIH NIH R01** · RUSH UNIVERSITY MEDICAL CENTER · 1991 · $175,738

## Abstract

The transduction of action potential to muscle contraction (EC
coupling) is an example of fast communication between cell membrane
events and metabolic state.  As in many systems, the central messenger of
this coupling is calcium, which in muscle is released from the
Sarcoplasmic Reticulum (SR) to activate contractile proteins.  The
release channels of the SR are controlled by changes in potential at the
plasma and T-tubular membrane.  The long term goal of this project is to
understand this control.  Since the last renewal of this grant, the
identity of two key molecular players, the voltage sensor of the T
membrane and the release channel of the SR, became known.  The central
problem of EC coupling -and of this proposal- can now be formulated as
understanding the interaction between the dihydropyridine receptor or
DHPr molecule (voltage sensor) and the ryanodine receptor or R Yr
(release channel).  A reductionist approach to this question will be
used, consisting of studies of the complete system and its parts.
          Measurements in the complete system will include intramembrane
charge movement (a manifestation of the voltage sensor) and Ca release
flux in single skeletal muscle cells.  A new voltage clamp technique will
improve previous measurements.  Understanding forward transmission will
require the elucidation of a newly found backward transmission: Ca
release feeds back on the voltage sensor.  Charge movement, Ca release,
and mechanisms of transmission will be unified in a comprehensive model
of EC coupling.  In this framework it will be possible to test
quantitatively two possible mechanisms of forward transmission:
mechanical, by direct or indirect contact between DHPr and RYr, or
chemical, via a diffusible transmitter.
          To study the parts of the system separately, two preparations
will be used: single channel recording with DHPrs and RYrs in bilayers
and measurement of Ca channel gating currents in heart cells.  A
comparison of the properties of the system and its parts will identify
properties that depend on the interaction, and help decide whether the
transmission is mechanical.  Promising preliminary work, in which an
interaction was demonstrated in bilayers by putting the components
together, will be continued and extended.
          The molecular mechanisms in E-C coupling are fundamentally
similar to other phenomena of membrane biophysics, and the key molecular
players are close isoforms of channel proteins found elsewhere.  Thus, in
addition to the obligatory relevance that the present studies should have
to the understanding of muscle dysfunction and therapeutics, findings in
Ec coupling should have a more general impact, on research of CNS
problems, heart and smooth muscle.

## Key facts

- **NIH application ID:** 3156409
- **Project number:** 2R01AR032808-09
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **SAM.gov UEI:** C155UU2TXCP3
- **Principal Investigator:** Eduardo Rios
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $175,738
- **Award type:** 2
- **Project period:** 1983-07-01 → 1996-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3156409

## Citation

> US National Institutes of Health, RePORTER application 3156409, CALCIUM MOVEMENTS IN EXCITATION-CONTRACTION COUPLING (2R01AR032808-09). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3156409. Licensed CC0.

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