# Molecular mechanisms underlying cardiac sodium channelopathy

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $396,603

## Abstract

Project Summary:
The cardiac voltage-gated sodium channel, NaV1.5, plays an important role in cardiac function. Genetic
mutations in NaV1.5 are known to be associated with various cardiac arrhythmias including long QT syndrome.
Our preliminary results suggested that NaV1.5 channel is regulated by cyclin-dependent kinase 5 (CDK5) and
that CDK5 and NaV1.5 channel are involved in cardiac arrhythmias caused by genetic mutations in the
CACNA1C calcium channel and MYH7 myofilament genes. The primary goal of this study is to unveil the
molecular mechanisms of cardiac NaV1.5 channel regulation and to elucidate the pathophysiological
mechanisms underlying cardiac arrhythmias associated with sodium channelopathy. Aim 1 is to examine how
CDK5 regulates NaV1.5 channels using human and mouse models with electrophysiological recordings. Aim 2
is to elucidate how cardiac sodium channel dysfunction results from the cardiac calcium channel mutants in
long QT syndrome type 8. Aim 3 is to test the hypothesis that CDK5 and NaV1.5 abnormalities are involved in
familial hypertrophic cardiomyopathy and arrhythmias that are caused by a familial MYH7 mutation. The
approaches of our study would provide new insights into the molecular basis of cardiac sodium channel
regulation and the pathophysiological mechanisms underlying cardiac arrhythmias with sodium channelopathy.

## Key facts

- **NIH application ID:** 9974589
- **Project number:** 5R01HL138486-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Masayuki Yazawa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $396,603
- **Award type:** 5
- **Project period:** 2017-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9974589

## Citation

> US National Institutes of Health, RePORTER application 9974589, Molecular mechanisms underlying cardiac sodium channelopathy (5R01HL138486-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9974589. Licensed CC0.

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