# BK potassium channel activity in cSiO2-induced lysosome membrane permeability and inflammation

> **NIH NIH F31** · UNIVERSITY OF MONTANA · 2021 · $37,823

## Abstract

Abstract
Chronic inflammation is a significant contributing factor to pulmonary and other diseases. One trigger of
chronic inflammation is respirable crystalline silica (cSiO2) in occupational settings, and, therefore, presents a
useful model to investigate the mechanisms of unresolved, lysosome dysfunction-mediated inflammation.
cSiO2 causes phagolysosomal membrane permeabilization (LMP) and NLRP3 inflammasome activation in
alveolar macrophages. The activated inflammasome cleaves caspase-1 and triggers inflammation through the
secretion of interleukin 1b (IL-1b) and interleukin 18 (IL-18). The lysosome’s role in NLRP3 inflammasome
activity and its contributions to macrophage homeostasis make it of significant interest in the development of
therapeutic targets for chronic inflammatory human health conditions. Within the lysosome, ion channels are
indispensable to its function. This research will investigate the role of the lysosomal potassium (K+) channel in
LMP and how it contributes to NLRP3-mediated inflammation. Current literature shows that particulate-induced
NLRP3 inflammasome activity correlates to a decrease in cytosolic K+, which is assumed to be K+ efflux from
the cytosol to the extracellular matrix. However, the contribution of lysosomal K+ channels to the decrease of
cytosolic K+ in NLPR3 inflammasome activation must be considered. Our preliminary results indicate that K+
movement into the lysosome through the lysosomal big conductance potassium (BK) channel precedes LMP
and NLRP3 inflammasome activity. Blocking lysosomal BK channel activity reduces cSiO2-induced cell death
and IL-1b release, suggesting lysosomal ion channel involvement in the mechanisms in LMP. This project will
address the hypothesis that cSiO2 interacts with the lysosomal membrane and initiates changes in the
lysosomal membrane lipid order and promotes lysosomal BK channel activity, a decrease in cytosolic K+, LMP,
and NLRP3 inflammasome activity.

## Key facts

- **NIH application ID:** 10314772
- **Project number:** 1F31ES033562-01
- **Recipient organization:** UNIVERSITY OF MONTANA
- **Principal Investigator:** Rebekah Kendall
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $37,823
- **Award type:** 1
- **Project period:** 2021-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10314772

## Citation

> US National Institutes of Health, RePORTER application 10314772, BK potassium channel activity in cSiO2-induced lysosome membrane permeability and inflammation (1F31ES033562-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10314772. Licensed CC0.

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