Nicotinic Receptor Subunits Atlas in the Adult Human Lung

Zania Diabasana,Julien Ancel,Myriam Polette,Philippe Gosset,Gonzague Delepine,Uwe Maskos,Randa Belgacemi,Pauline Mulette,Gaëtan Deslée,Valérian Dormoy,Jeanne-Marie Perotin

doi:10.3390/ijms21207446

Abstract

Nicotinic acetylcholine receptors (nAChRs) are pentameric ligand-gated ion channels responsible for rapid neural and neuromuscular signal transmission. Although it is well documented that 16 subunits are encoded by the human genome, their presence in airway epithelial cells (AECs) remains poorly understood, and contribution to pathology is mainly discussed in the context of cancer. We analysed nAChR subunit expression in the human lungs of smokers and non-smokers using transcriptomic data for whole-lung tissues, isolated large AECs, and isolated small AECs. We identified differential expressions of nAChRs in terms of detection and repartition in the three modalities. Smoking-associated alterations were also unveiled. Then, we identified an nAChR transcriptomic print at the single-cell level. Finally, we reported the localizations of detectable nAChRs in bronchi and large bronchioles. Thus, we compiled the first complete atlas of pulmonary nAChR subunits to open new avenues to further unravel the involvement of these receptors in lung homeostasis and respiratory diseases.

Highlights

Nicotinic acetylcholine receptors are ligand-gated proteins expressed in the brain and non-neuronal cells, including lung airway epithelial cells (AECs), macrophages, neutrophils, and muscle cells [1]
Considering the whole lung contains all types of tissues, including epithelia, muscle, connective, and nervous tissues (Figure 1a), the 16 Nicotinic acetylcholine receptors (nAChRs) were detected among non-smoker subjects except for CHRNA7, which was consistent in both datasets containing non-smokers (Figure 1b and Supplemental Table S1)
The global repartition in non-smokers and smokers favoured CHRNA10/B1/E, representing almost half of all nAChR subunits expressed in lung tissues (Figure 1c and Supplemental Table S2)

Summary

Introduction

Nicotinic acetylcholine receptors (nAChRs) are ligand-gated (cation-permeable) proteins expressed in the brain and non-neuronal cells, including lung airway epithelial cells (AECs), macrophages, neutrophils, and muscle cells [1]. These receptors are composed of five subunits organized as homo- or hetero-pentamers forming a channel permeable to monovalent and divalent cations (predominantly Na+, K+, and Ca2+) [1,2]. Homomeric α7 and heteromeric α4/β2 subtypes are abundantly detected and are known to play an important role in memory and learning due to their predominance in the hippocampal and cortical neurons [11,12]. The diversity of nAChRs confers differential affinities to the ligands affecting several parameters, including the channel opening and closing duration, the modulation of ionic conductance, and cationic selectivity [1,2,12,14]

Methods

Results

Conclusion