# Structure-function studies on Ion channels

> **NIH NIH R35** · OREGON HEALTH & SCIENCE UNIVERSITY · 2024 · $407,496

## Abstract

Project Summary:
Our research program investigates the functional mechanisms that operate in voltage gated K+ (Kv) channels.
Kv channels are essential for the generation and conduction of electrical signals by neurons, muscles and
endocrine cells. Underlying the physiological roles of Kv channels is their ability to regulate the flux of K+ across
cellular membranes. The flux of K+ through a Kv channel is controlled by the processes of voltage activation,
which turns on the flux, and inactivation, which turns off the flux of K+ through the channel. There have been
extensive investigations on Kv channels but major questions remain on the activation and inactivation
mechanisms. In our research program, we use a multidisciplinary approach that combines structural and
functional studies with protein modifications using unnatural amino acid (UAA) mutagenesis. UAA mutagenesis
is a very powerful method for protein modification compared to traditional mutagenesis because it allows a large
variety of side chain modifications and permits the modification of the protein backbone. In the grant period, we
will investigate C-type inactivation in the Shaker, Kv1.2 and the cardiac Kv channel HERG. C-type inactivation
refers to a conformational change at the selectivity filter, the ion binding region of the channel, that turns off the
flux of ions through the channel. We will also investigate the role of the protein main chain interactions in voltage
gating. Our studies on voltage gating will be carried out in the hyperpolarization activated and cyclic nucleotide
gated ion (HCN) channel. The research proposed is significant because it will provide key mechanistic insights
into the working of Kv channels. The research will also provide strategies for investigating the role of the protein
backbone and ion binding sites, strategies that will be generally applicable to other ion channels.

## Key facts

- **NIH application ID:** 10842034
- **Project number:** 1R35GM153212-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Francis Valiyaveetil
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $407,496
- **Award type:** 1
- **Project period:** 2024-04-01 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10842034

## Citation

> US National Institutes of Health, RePORTER application 10842034, Structure-function studies on Ion channels (1R35GM153212-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10842034. Licensed CC0.

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