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Cigarette Smoke Disrupts Calcium Homeostasis in Airway Smooth Muscle Cells
Author(s) -
Lin Jinheng,
Taggart Michael,
Tarran Robert,
Gray Michael
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.734.11
Subject(s) - calcium , calcium metabolism , chemistry , endocrinology , medicine , contractility , homeostasis , extracellular , calcium in biology , biochemistry
Tobacco smoking is the largest risk factor for developing chronic obstructive pulmonary disease (COPD), and is associated with airway hyperresponsiveness. Hyperresponsiveness is linked to abnormal calcium metabolism, which regulates the contractility and hence the tone of airway smooth muscle (ASM). However, whether cigarette smoke (CS) directly alters or regulates calcium signaling in ASM cells (ASMC) is not fully known. In airway epithelial cells, acute CS exposure increases intracellular Ca 2+ concentrations ([Ca 2+ ] i ). We hypothesise that CS impedes ASM function by disrupting calcium homeostasis in ASMC, and the present study aims to unravel the effects of CS on calcium handling in ASMC. Primary rat and human ASMC were isolated via enzymatic digestion, and maintained in culture up to 8 passages. ASMC were seeded onto glass coverslips, and deprived of serum for 24–48 hours prior to calcium imaging studies using fura‐2‐AM. ASMC were exposed to either whole CS or CS extract (CSE) from 3R4F reference cigarettes (University of Kentucky) with the particulate phase filtered out. We found that both CS and CSE elevated [Ca 2+ ] i in rat and human ASMC, and this increase was not abolished following depletion of sarcoplasmic‐reticulum calcium stores with thapsigargin or cyclopiazonic acid. The increase in [Ca 2+ ] i in response to CSE was concentration‐dependent. Removal of extracellular calcium attenuated the CSE‐induced elevation of [Ca 2+ ] i in hASMC, suggesting that CSE may activate calcium influx pathways in cultured hASMC. We speculate that this elevation of [Ca 2+ ] i would lead to exacerbated ASM contraction, especially under inflamed conditions in COPD, and hence narrowing of the airway lumen. Further investigations into the source of [Ca 2+ ] i increase, identity of potential calcium influx channels activated, and the direct effects of CS/CSE on ASM contraction are on‐going. Support or Funding Information This work is supported by Newcastle University's JJ Hunter Bequest scholarship. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .