# Biophysical Modulation of Cardiac Ion Channels by MicroRNA

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2020 · $619,298

## Abstract

Project Summary
MicroRNAs (miRs) are small non-coding RNA molecules (~22 nucleotides) known to negatively regulate gene
expression through RNA silencing and post-transcriptional regulation. Importantly, miRs are increasingly
recognized for the maintenance of cardiac function, modulation of cardiac excitability, and the development of
disease states through their classical mechanism of finely controlling the expression of target genes. miR1 is
the most predominant miR in the heart and plays a critical role for cardiovascular development and cardiac
electrophysiology. In this study, we questioned whether this regulation of cardiac function was solely due to the
classical mechanism of miRs or if this could also be attributed to a novel role for miR1 mediated through its
physical interaction with cardiac proteins. We first performed an in vitro electron mobility shift assay (EMSA) to
investigate if miR1 and miR451a, which are both highly expressed in the heart, can bind with membrane
proteins extracted from neonatal and adult mouse hearts. Remarkably, we found that miR1, but not miR451a,
could specifically bind with membrane proteins and identified that Kir2.1, an inward rectifier potassium channel,
was one of the membrane proteins that miR1 binds to. To establish the potential biophysical consequence of
this binding, we performed patch clamp recordings of inward rectifier potassium current (IK1) and delivered
miR1 acutely to bypass the transcriptome regulation. Importantly, we found that the current density of IK1 was
significantly suppressed by acute expression of miR1. To our knowledge, this is the first discovery of the novel
and groundbreaking concept that miRs physically interact with ion channels to modulate their biophysical
function. Hence the overall hypothesis of this proposal is that miR1 can also regulate cardiac excitability
through direct interaction with cardiac ion channels. Therefore, we propose to investigate the mechanism of
miR1-ion channel interaction with the following aims: 1. Define the physical interaction between miR1 and
Kir2.1. 2. Evaluate the functional implications of the physical interaction between miR1 and Kir2.1. 3. Identify
other cardiac ion channels that physically interact with and are modulated by miR1. Several approaches will be
used to identify the ion channels that miR1 interacts with. Importantly, we will investigate the physiological role
of this physical interaction in expression systems and in cardiomyocytes. We will study the electrophysiology of
cardiomyocytes by patch-clamp with acutely-delivered miR1 to investigate how miR1 modulates cardiac
electrophysiology without its transcriptome effect. Our study will provide a mechanistic understanding of how
miR1 physically binds with ion channels and directly regulates their functions. We will also investigate if this
physical interaction between miR1 and Kir2.1 is a general function of miRs by identifying more miR1-bound ion
channels. A better understanding ...

## Key facts

- **NIH application ID:** 10137427
- **Project number:** 7R01HL139006-04
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Isabelle Deschenes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $619,298
- **Award type:** 7
- **Project period:** 2017-07-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10137427

## Citation

> US National Institutes of Health, RePORTER application 10137427, Biophysical Modulation of Cardiac Ion Channels by MicroRNA (7R01HL139006-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10137427. Licensed CC0.

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