Contribution of Val/Ile87 residue in the extracellular domain in agonist-induced current responses of the human and rat P2X7 receptors

Purinergic signalling

article

Emily A Caseley¹  Stephen P Muench²  Lin-Hua Jiang² 

[1] Leeds Institute of Rheumatic and Musculoskeletal Medicine, St James’s University Hospital, Faculty of Medicine and Health;School of Biomedical Sciences, Faculty of Biological Sciences, University of Leeds

关键词: P2X7 receptor;    Species difference;    Agonist-induced currents;    Whole-cell recording;   

DOI  :  10.1007/s11302-020-09730-1

学科分类：分子生物学，细胞生物学和基因

来源: Springer

【 摘 要 】

The P2X7 receptor (P2X7R) is an ATP-gated cation channel with a critical role in many physiological and pathological processes, and shows prominent functional differences across mammalian species, exemplified by larger current responses of the rat (r) P2X7R to ATP and its analogue BzATP and a greater sensitivity to agonists compared with the human (h) P2X7R. Here, we showed that substitution of Val87 residue in the extracellular domain of the hP2X7R with isoleucine in the rP2X7R increased the current responses of the hP2X7R to both ATP and BzATP. Conversely, introduction of reciprocal I87V mutation in the rP2X7R led to a noticeable but statistically insignificant reduction in the current responses of the rP2X7R to ATP and BzATP. The mutations did not affect the sensitivity of the human and rat P2X7Rs to ATP and BzATP. These results suggest a contribution of Val/Ile87 in agonist-induced current responses of human and rat P2X7Rs, which helps to better understand the molecular determinants for species-dependent function of the mammalian P2X7Rs.

【 授权许可】

CC BY