E-Cigarette Aerosols of Propylene Glycol Impair BK Channel Activity and Parameters of Mucociliary Function

Authors

Michael D Kim
Samuel Chung
Nathalie Baumlin
Liang Sun
Neerupma Silswal
John S Dennis
Makoto Yoshida
Juan Sabater
Frank T Horrigan
Matthias Salathe

Publication Date

4-1-2023

Journal

American Journal of Physiology Lung Cellular and Molecular Physiology

DOI

10.1152/ajplung.00157.2022

PMID

36809074

PMCID

PMC10042605

PubMedCentral® Posted Date

2-21-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Animals, Sheep, Electronic Nicotine Delivery Systems, Large-Conductance Calcium-Activated Potassium Channels, Magnesium Oxide, Aerosols, Propylene Glycols

Abstract

Propylene glycol (PG) is a common delivery vehicle for nicotine and flavorings in e-cigarette (e-cig) liquids and is largely considered safe for ingestion. However, little is known about its effects as an e-cig aerosol on the airway. Here, we investigated whether pure PG e-cig aerosols in realistic daily amounts impact parameters of mucociliary function and airway inflammation in a large animal model (sheep) in vivo and primary human bronchial epithelial cells (HBECs) in vitro. Five-day exposure of sheep to e-cig aerosols of 100% PG increased mucus concentrations (% mucus solids) of tracheal secretions. PG e-cig aerosols further increased the activity of matrix metalloproteinase-9 (MMP-9) in tracheal secretions. In vitro exposure of HBECs to e-cig aerosols of 100% PG decreased ciliary beating and increased mucus concentrations. PG e-cig aerosols further reduced the activity of large conductance, Ca2+-activated, and voltage-dependent K+ (BK) channels. We show here for the first time that PG can be metabolized to methylglyoxal (MGO) in airway epithelia. PG e-cig aerosols increased levels of MGO and MGO alone reduced BK activity. Patch-clamp experiments suggest that MGO can disrupt the interaction between the major pore-forming BK subunit human Slo1 (hSlo1) and the gamma regulatory subunit LRRC26. PG exposures also caused a significant increase in mRNA expression levels of MMP9 and interleukin 1 beta (IL1B). Taken together, these data show that PG e-cig aerosols cause mucus hyperconcentration in sheep in vivo and HBECs in vitro, likely by disrupting the function of BK channels important for airway hydration.

Comments

This article has been corrected. See Am J Physiol Lung Cell Mol Physiol. 2023 Jun 1;324(6):L886.

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