Nicotine elevated intracellular Ca2+ in rat airway smooth muscle cells via activating and up-regulating α7-nicotinic acetylcholine receptor

Yongliang Jiang, Aiguo Dai, Yumin Zhou, Gongyong Peng, Guoping Hu, Bing Li, James Sham, Pixin Ran

Research output: Contribution to journalArticle

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is characterized by airway remodeling with airway smooth muscle (ASM) hypertrophy and hyperplasia. Since tobacco use is the key risk factor for the development of COPD and intracellular Ca2+ concentration ([Ca2+] i) plays a major role in both cell proliferation and differentiation, we hypothesized that nicotinic acetylcholine receptor (nAChR) activation plays a role in the elevation of [Ca2+]i in airway smooth muscle cells (ASMCs). Methods: We examined the expression of nAChR and characterized the functions of α7-nAChR in ASMCs. Results: RT-PCR analysis showed that α2-7, β2, and β3-nAChR subunits are expressed in rat ASMCs, with α7 being one of the most abundantly expressed subtypes. Chronic nicotine exposure increased α7-nAChR mRNA and protein expression, and elevated resting [Ca2+]i in cultured rat ASMCs. Acute application of nicotine evoked a rapid increase in [Ca2+]i in a concentration-dependent manner, and the response was significantly enhanced in ASMCs cultured with 1 μM nicotine for 48 hours. Nicotine-induced Ca 2+ response was reversibly blocked by the α7-nAChR nicotinic antagonists, methyllycaconitine and α-bungarotoxin. Small interfering RNA suppression of α7-nAChR also substantially blunted the Ca2+ responses induced by nicotine. Conclusion: These observations suggest that nicotine elevates [Ca2+]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.that nicotine elevates [Ca2+]i in ASMCs through α7-nAChR-mediated signals pathways, and highlight the possibility that α7-nAChR can be considered as a potential target for the treatment of airway remodeling.

Original languageEnglish (US)
Pages (from-to)389-401
Number of pages13
JournalCellular Physiology and Biochemistry
Volume33
Issue number2
DOIs
Publication statusPublished - 2014

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Keywords

  • Airway smooth muscle cells
  • Intracellular calcium
  • Nicotine
  • Nicotinic acetylcholine receptors

ASJC Scopus subject areas

  • Physiology

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