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.

P2X7 受体 (P2X7R) 是一种 ATP 门控阳离子通道，在许多生理和病理过程中起着关键作用，并且在哺乳动物物种之间显示出显着的功能差异，例如大鼠 (r) P2X7R 对 ATP 及其类似物的较大电流反应与人 (h) P2X7R 相比，BzATP 和对激动剂的敏感性更高。在这里，我们表明用 rP2X7R 中的异亮氨酸替换 hP2X7R 细胞外结构域中的 Val87 残基增加了 hP2X7R 对 ATP 和 BzATP 的当前反应。相反，在 rP2X7R 中引入互惠 I87V 突变导致 rP2X7R 对 ATP 和 BzATP 的当前反应显着但统计学上不显着的降低。突变不影响人和大鼠 P2X7Rs 对 ATP 和 BzATP 的敏感性。