# SLO family potassium channels: function and physiology

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2021 · $711,542

## Abstract

Abstract
The calcium and voltage regulated BK(or SLO1)-type K+ channel is a widely expressed ion channel impacting
on regulation of excitability in a variety of both excitable and inexcitable tissues. SLO1 is encoded by the
kcnma1(or slo1) gene, one of four SLO family members. The ability of SLO family channels to be regulated by
specific cytosolic ions arises from a large cytosolic regulatory domain, containing specific ion binding sites, that
is connected to the pore-forming part of the subunits. The ability of SLO family channels to respond to changes
in the cytosolic milieu makes them uniquely adapted to play negative feedback roles following activity that
leads to alterations in the cytosolic ions. The Ca-regulated BK channel is particularly fascinating, since despite
being encoded by a single gene, it is expressed in a wide variety of cells in each case playing very distinct
physiological roles. A central tenet of the work in this laboratory is that the functional diversity and the
associated broad scope of physiological roles played by BK channels arises from associated with regulatory
subunits. For BK channels, tissue-specific expression of up to four different regulatory  subunits (1-4) and
four  subunits can define BK function and physiology. Our understanding of the loci of expression, channel
composition in particular cells, and the impact of particular regulatory subunits on function and physiology
remains rudimentary. and 4 subunits have been implicated in hypertension and epilepsy, respectively, and
other indications suggest that BK channels may be therapeutic targets in stroke, hypertension, epilepsy, and
tumor growth regulation. To address the gaps in understanding of the roles of BK channels of particular subunit
composition, this lab combines methods ranging from biophysical analysis of channel properties to the use of
genetic knock-out (KO) of specific regulatory subunits. This permits evaluation not only of the biophysical and
functional properties of channels of different auxiliary subunit composition in native cells, but also how these
channels contribute to physiological roles. Furthermore, we continue to probe questions of BK channel function
pertinent to channel inactivation mechanisms and stoichiometry, guided by available structural information.
Recent work on animal models developed in this lab have established important roles of 1 and 2 subunits in
defining BK channel functions in secretory epithelial cells and inner hair cells, respectively, while -containing
BK channels influence action potential firing rates and burst behavior. Future work will further probe our
existing models, e.g., the role of 1-containing BK channels in colonic epithelium. In addition, a major focus will
be the development of animal models that will allow examination of 3-containing BK currents in native cells.
3-containing BK channels remain the least understood of all BK channel subunits and we seek to remedy that
deficit. Thi...

## Key facts

- **NIH application ID:** 10167469
- **Project number:** 2R35GM118114-06
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Christopher J Lingle
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $711,542
- **Award type:** 2
- **Project period:** 2016-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10167469

## Citation

> US National Institutes of Health, RePORTER application 10167469, SLO family potassium channels: function and physiology (2R35GM118114-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10167469. Licensed CC0.

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