# Potassium Channels and Control of Cardiovascular Function

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2020 · $915,000

## Abstract

ABSTRACT
My lab studies the mechanistic basis, and functional consequences, of ion channels, particularly background
inward rectifier and ATP-sensitive potassium channels, that are found throughout the cardiovascular system.
Our work integrates studies at multiple levels, from the fundamental molecular basis of channel activity to
animal models of pathologies associated with human disease. We are interested in how channels are
constructed and function, how they regulate individual smooth and cardiac muscles, and how altered channel
function contributes to the pathological consequences of aberrant function in the cardiovascular system.
Previously, we discovered that soluble cytoplasmic polyamines cause inward rectification and demonstrated their
mechanism and sites of action in Kir channels. We have developed the capability to purify Kir and ATP-sensitive
(KATP) channels and to analyze these proteins structurally, biochemically and functionally. This allows us to
develop and address exciting new questions and hypotheses regarding the fundamental basis of Kir and KATP
channel activity, including the molecular mechanisms by which lipids regulate gating and the dynamic structural
changes that accompany gating. KATP channels link metabolism to electrical activity in cardiac and smooth muscle.
Our recent findings regarding a causal role of KATP channel mutations in human Cantu Syndrome (CS) reveal
multiple pathological consequences of underexcitability, including persistence of fetal circulation, pericardial
effusion, lymphedema, decreased vascular compliance and decreased gut motility. Development of unique and
novel genetically modified animals, as well as a unique research CS clinic, has allowed us to generate extensive
preliminary data that begin to explain such features, and leads us to novel hypotheses which will be explored
using multiple cell biological and physiological approaches in animals and humans to reach a full understanding of
the nature and role of KATP dependent excitability in regulation of cardiovascular function. These studies will form
the background to the testing of relevant pharmacological approaches to CS therapy in animal models and in
humans, with the ultimate goal of developing a specific therapy for CS and related pathologies.

## Key facts

- **NIH application ID:** 9869031
- **Project number:** 5R35HL140024-03
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Colin G Nichols
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $915,000
- **Award type:** 5
- **Project period:** 2018-01-01 → 2024-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9869031

## Citation

> US National Institutes of Health, RePORTER application 9869031, Potassium Channels and Control of Cardiovascular Function (5R35HL140024-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9869031. Licensed CC0.

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