# Discovery and mechanism of BK channel gating modulators

> **NIH NIH R01** · TEMPLE UNIV OF THE COMMONWEALTH · 2020 · $317,000

## Abstract

PROJECT SUMMARY
 Large conductance calcium-activated K channels (SLO-1 or BK channels) play a key physiological
role in controlling activity of nerve and smooth muscle, as well as setting the resting membrane
potential in epithelial cells. 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, and BK channels are upregulated in prostate and other cancers. Selective BK
channel activators, as well as inhibitors, could thus become components of treatment regimens for
cardiovascular/neurological disease and brain and prostate cancers. To exploit BK channels as a
potential medical target, it will be important to expand our molecular arsenal of BK channel activators
and inhibitors 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 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 computational and 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. Our proposed research will
generate new pharmacological research tools to modulate BK channels, which will be combined with
established strengths in quantitative electrophysiological analysis, to gain fundamental insights
toward BK channel gating mechanisms that may further lead to new treatments for disease.

## Key facts

- **NIH application ID:** 9948686
- **Project number:** 5R01GM126581-03
- **Recipient organization:** TEMPLE UNIV OF THE COMMONWEALTH
- **Principal Investigator:** Brad S. Rothberg
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $317,000
- **Award type:** 5
- **Project period:** 2018-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9948686

## Citation

> US National Institutes of Health, RePORTER application 9948686, Discovery and mechanism of BK channel gating modulators (5R01GM126581-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9948686. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*