# Opto-Electrophysiological Method to Study Human Skeletal Muscle Channelopathies

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $154,440

## Abstract

ABSTRACT
Myopathies stemming from mutations in genes coding for ion channels or proteins that regulate their pre-RNA
splicing are called, respectively, channelopathies and spliceopathies. Abnormal expression, structure or function
of ion channels resulting from those mutations leads to altered muscle electrophysiology and excitation-
contraction coupling. These genetic disorders have currently no cure, severely affect the quality of life of patients
and span the prevalence spectrum from rare diseases (e.g. hypo- and hyperkalemic periodic paralysis, 1:100000)
to the most common myopathies (e.g. dystrophic myotonia, 1-5:10000). While their genetic cause is readily
identifiable, understanding the mechanisms underlying channelopathies and spliceopathies, and designing
sound therapeutic strategies for them, demands detailed electrophysiological studies performed in the all-
meaningful human cellular context. These studies, though feasible, are impeded by a pervasive lack of practical,
high throughput methods amenable for use in human muscles. Animal models used to circumvent this
shortcoming often fail to recapitulate most diseases or to reproduce the human response to therapeutic drugs.
We intend to overcome these limitations by designing and testing a novel, practical electrophysiological method
facilely used with human muscle fibers dissected from biopsies. We will combine a revolutionary experimental
chamber with technologies from two different electrophysiological methods to perform quantitative, state of the
art, electrophysiological studies in segments of fibers 50-400μm long in near-ideal conditions. Unlike previous
methods, this new method is readily implemented, user-friendly, and affords the requisite high throughput for
statistically significant studies. Our method will allow case-by-case electrophysiological studies and screening of
acutely acting drugs, enabling the design of patient specific treatment schemes, coinciding with current trends
in contemporary precision medicine. We expect, then, our method will have a transformative impact in human
muscle physiology and pathophysiology.

## Key facts

- **NIH application ID:** 10596561
- **Project number:** 5R21AR080282-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Marino Di Franco
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $154,440
- **Award type:** 5
- **Project period:** 2022-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10596561

## Citation

> US National Institutes of Health, RePORTER application 10596561, Opto-Electrophysiological Method to Study Human Skeletal Muscle Channelopathies (5R21AR080282-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10596561. Licensed CC0.

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