Functional α7 nicotinic receptors in human airway smooth muscle increase intracellular calcium concentration and contractility in asthmatics.

Autor: Khalfaoui, Latifa, Mukhtasimova, Nuriya, Kelley, Brian, Wells, Natalya, Teske, Jacob J., Roos, Benjamin B., Borkar, Niyati A., Zhang, Emily Y., Sine, Steven M., Prakash, Y. S., Pabelick, Christina M.
Předmět:
Zdroj: American Journal of Physiology: Lung Cellular & Molecular Physiology; Jul2023, Vol. 325 Issue 1, pL17-L29, 13p
Abstrakt: Although nicotinic acetylcholine receptors (nAChRs) are commonly associated with neurons in the brain and periphery, recent data indicate that they are also expressed in non-neuronal tissues. We recently found the alpha7 (α7nAChR) subunit is highly expressed in human airway smooth muscle (hASM) with substantial increase in asthmatics, but their functionality remains unknown. We investigated the location and functional role of α7nAChRs in hASM cells from normal versus mild-moderate asthmatic patients. Immunostaining and protein analyses showed α7nAChR in the plasma membrane including in asthmatics. In asthmatic hASM, patch-clamp recordings revealed significantly higher functional homomeric α7nAChR channels. Real-time fluorescence imaging showed nicotine, via α7nAChR, increases intracellular Ca2+ ([Ca2+]i) independent of ACh effects, particularly in asthmatic hASM, while cellular traction force microscopy showed nicotine-induced contractility including in asthmatics. These results indicate functional homomeric and heteromeric nAChRs that are increased in asthmatic hASM, with pharmacology that likely differ owing to different subunit interfaces that form the orthosteric sites. nAChRs may represent a novel target in alleviating airway hyperresponsiveness in asthma. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index