# The Structural Basis of Antiarrhythmic Drug Binding in Voltage-gated Ion Channels

> **NIH NIH K08** · UNIVERSITY OF WASHINGTON · 2020 · $163,148

## Abstract

Abstract/Project Summary
 Cardiac arrhythmias affect millions of Americans and are a common cause
of morbidity and mortality in older Americans, as well as health care
expenditures. They have many causes including inherited gene mutations,
electrolyte disturbances, and drug side effects—though all of these causes share
the misfiring of voltage-gated ion channels in myocardium. Anti-arrhythmic
drugs (AAD) are widely used to treat both atrial and ventricular arrhythmias by
blocking such channels, though there is currently a limited understanding of the
AAD molecular mechanism of action on a structural level. In this proposal, I aim
to study AADs in model voltage-gated sodium and calcium channels, using the
widely used sodium channel blocker AAD lidocaine and flecainide as well as the
widely used calcium channel blocker AAD diltiazem. I will use established
techniques of electrophysiology and X-ray crystallography to study AAD in
complex with bacterial voltage-gated sodium and calcium channels, while
working to establish new structural models of the AAD binding site using
concatenated bacterial channels, higher order channels, and Cryo-EM methods. I
expect these experiments to allow for a better understanding of voltage-gated ion
channel physiology and aid in the design of safer and more effective AAD, as well
as novel therapeutics that may be used for treatment of atrial and ventricular
arrhythmias.

## Key facts

- **NIH application ID:** 9853845
- **Project number:** 5K08HL145630-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** MICHAEL J LENAEUS
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $163,148
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853845

## Citation

> US National Institutes of Health, RePORTER application 9853845, The Structural Basis of Antiarrhythmic Drug Binding in Voltage-gated Ion Channels (5K08HL145630-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853845. Licensed CC0.

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