# Ion Channel Transporter Interactions

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA-IRVINE · 2020 · $417,150

## Abstract

Project Summary
Voltage-gated potassium (Kv) channels are generated by tetramers of pore-forming α subunits, often in
complexes with other, non-pore-forming β subunits. This project is focused on two highly important, 5-member
families of Kv channel subunits: the KCNQ α subunits and the KCNE β subunits. KCNQ1 is essential in the
heart and numerous epithelia; its diverse physiological roles in both excitable and non-excitable cells are
facilitated by interaction with each of the 5 KCNE single-transmembrane domain β subunits. KCNE β subunits
are widely expressed and regulate α subunits from most Kv subfamilies, and even other channel types.
KCNQ2-5 α subunits, especially KCNQ2/3 heteromers, are best known for their essential role in generating the
neuronal M-current, which regulates neuronal excitability. KCNQ2-5 are also expressed in other tissues,
including the vasculature and auditory system. Reflecting their physiologic importance, disruption of KCNQ or
KCNE genes causes disorders as diverse as cardiac arrhythmia, diabetes, achlorhydria, hypothyroidism, and
epilepsy. We use a highly integrated approach to investigate the molecular mechanistic bases for KCNQ and
KCNE biology and pathophysiology. This includes both knockout and knock-in mouse models, cellular
electrophysiology, transport and radioligand assays, transcriptomics, various imaging modalities, structure-
function and biochemical techniques. In the next five years, we aim to address several outstanding challenges
in the field, pursuing the following novel research directions. (1) Inherited disorders linked to KCNQ or KCNE
genes are often highly complex, multi-system diseases because the genes are typically expressed in multiple
tissues. Yet, traditional approaches often involve focusing on a single tissue. We aim to dissect the basis for
KCNQ- and KCNE-based diseases by embracing multi-system approaches and by first understanding the
molecular basis for the intertwining physiological functions of these subunits. (2) We recently found that KCNQ
channels form physiologically essential complexes with several different types of sodium-coupled solute
transporters. We will study the molecular mechanisms and roles of novel signaling nanodomains created by
“chansporter” complexes. (3) We very recently discovered that some neurotransmitters and their analogs can
directly activate specific neuronal KCNQs, a paradigm shift with potentially widespread ramifications. We will
investigate its physiological relevance, molecular mechanisms, and crosstalk with co-assembled transporters.
(4) We will pursue the molecular basis and physiological importance of several newly discovered KCNQ and
KCNE interactions involving, e.g., Amyloid Precursor Protein C99 fragment, and the focal adhesion protein,
Testin. Work in this project will dissect the rich repertoire of signaling facilitated by ion channels containing
KCNQ and/or KCNE subunits, in a variety of different organ systems and cell types. The goals are t...

## Key facts

- **NIH application ID:** 9851411
- **Project number:** 5R35GM130377-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA-IRVINE
- **Principal Investigator:** Geoffrey W Abbott
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $417,150
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9851411

## Citation

> US National Institutes of Health, RePORTER application 9851411, Ion Channel Transporter Interactions (5R35GM130377-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9851411. Licensed CC0.

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