# Discovery and mechanism of BK channel gating modulators

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2021 · $84,207

## Abstract

PROJECT SUMMARY
 Large conductance calcium-activated K channels (SLO-1 or BK channels) play a key
physiological role in limiting smooth muscle contractility and neuronal excitability. Deletion of BK
channel pore-forming (alpha) or modulatory (beta) subunits in gene-targeted animal models can
lead to diseases that include arterial hypertension, bladder and erectile dysfunction, and
neurological disorders including epilepsy; mutations in human BK channel subunits are linked to
generalized epilepsy with paroxysmal dyskinesia (GEPD), asthma, and autism spectrum
disorders. BK channel activators could thus become components of treatment regimens for
cardiovascular and/or neurological disease. To exploit BK channels as a potential medical
target, it will be important to expand our molecular arsenal of BK channel activators and learn
their mechanisms of action. Doing so will lead to advances in an overall effort to understand BK
channel gating mechanisms and ultimately find new treatments for cardiovascular and
neurological disease. Under this proposal, we will achieve these goals through a combination of
1) cell-based fluorescent screening, which is aimed at discovery of novel gating modulators for
BK channels comprised of tissue-specific subunit combinations, and 2) systematic
electrophysiological experiments to determine whether these drugs modulate BK channel
function through interactions with the Ca2+-sensor, voltage-sensor, or pore domains of the
channel.
 This equipment supplement will be used for purchase of an isothermal titration calorimeter
(ITC) that is capable of directly determining thermodynamic binding constants in drug-receptor
interactions. This tool will greatly enhance our research to yield fundamental insights toward BK
channel gating mechanisms that may further lead to new treatments for disease.

## Key facts

- **NIH application ID:** 10388686
- **Project number:** 3R01GM126581-04S1
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Brad S. Rothberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $84,207
- **Award type:** 3
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10388686

## Citation

> US National Institutes of Health, RePORTER application 10388686, Discovery and mechanism of BK channel gating modulators (3R01GM126581-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10388686. Licensed CC0.

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