# Genetic and chemical biological studies of K2P structure, function, andmodulation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2022 · $787,509

## Abstract

Project Summary
The long-term goals of this project are to develop an understanding of the fundamental mechanisms that control
the function of K2P potassium channels and to identify, develop, and characterize small molecule, ion channel
modulators for the K2P family. K2Ps are a diverse family of potassium-selective channels that are responsible for
background ‘leak’ currents. These currents are pivotal in modulating the excitability of neurons. K2Ps respond to
varied stimuli that include pH changes, temperature, and mechanical force. Although K2Ps have well-established
roles in the nervous and cardiovascular systems and are implicated in pain, anesthetic responses,
thermosensation, and mood, they remain the least well-understood potassium channel class. Ion channels are
coveted drug targets. As membrane proteins, they are readily accessible to extracellular compounds and their
modulation brings about rapid changes in the properties of excitable cells in the heart and brain. However, as
membrane proteins, they also reside beyond many well-established approaches for modulator development.
Consequently, many channels, including those in the K2P family, lack significant pharmacologies. This problem
leads to a gap in our ability to connect ion channel genes with in vivo function. We are pursuing a
multidisciplinary approach that includes biophysical, structural, computational, and electrophysiological
measurements and chemical biology approaches to identify, dissect, and characterize the core elements that
control K2P function and to define and characterize new small molecules that can control K2P activity. Defining
the molecular mechanisms that control K2p activity and uncovering new K2P modulators should provide the key
framework and necessary tools for understanding how K2Ps function. Because of their important roles in human
physiology, K2Ps are targets for drugs for the treatment of chronic pain, stroke, and depression. Thus, developing
an understanding of how K2Ps function and small molecules that affect channel function should not only provide
powerful tools for dissecting K2P mechanism but should aid in the development of new therapeutic agents for a
range of human diseases.

## Key facts

- **NIH application ID:** 10444595
- **Project number:** 2R01MH093603-11A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** DANIEL L MINOR
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $787,509
- **Award type:** 2
- **Project period:** 2011-03-01 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10444595

## Citation

> US National Institutes of Health, RePORTER application 10444595, Genetic and chemical biological studies of K2P structure, function, andmodulation (2R01MH093603-11A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10444595. Licensed CC0.

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