Rudolf-Boehm-Institut für Pharmakologie und Toxikologie, University of Leipzig, Leipzig, 04107, Germany.
Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, 610075, China.
Nat Commun. 2018 Apr 10;9(1):1354. doi: 10.1038/s41467-018-03728-5.
Two subclasses of acid-sensing ion channels (ASIC3) and of ATP-sensitive P2X receptors (P2X3Rs) show a partially overlapping expression in sensory neurons. Here we report that both recombinant and native receptors interact with each other in multiple ways. Current measurements with the patch-clamp technique prove that ASIC3 stimulation strongly inhibits the P2X3R current partly by a Ca-dependent mechanism. The proton-binding site is critical for this effect and the two receptor channels appear to switch their ionic permeabilities during activation. Co-immunoprecipation proves the close association of the two protein structures. BN-PAGE and SDS-PAGE analysis is also best reconciled with the view that ASIC3 and P2X3Rs form a multiprotein structure. Finally, in vivo measurements in rats reveal the summation of pH and purinergically induced pain. In conclusion, the receptor subunits do not appear to form a heteromeric channel, but tightly associate with each other to form a protein complex, mediating unidirectional inhibition.
两种酸感应离子通道（ASIC3）亚类和三磷酸腺苷敏感的 P2X 受体（P2X3Rs）在感觉神经元中表现出部分重叠的表达。在这里，我们报告说，重组和天然受体以多种方式相互作用。用膜片钳技术进行的电流测量证明，ASIC3 刺激强烈抑制 P2X3R 电流，部分原因是 Ca 依赖性机制。质子结合位点对于这种效应至关重要，并且这两个受体通道在激活过程中似乎改变它们的离子通透性。共同免疫沉淀证明了两种蛋白质结构的密切关联。BN-PAGE 和 SDS-PAGE 分析也最好与 ASIC3 和 P2X3Rs 形成多蛋白结构的观点相一致。最后，在大鼠体内测量揭示了 pH 和嘌呤能诱导疼痛的总和。总之，受体亚基似乎没有形成异源通道，而是彼此紧密结合形成蛋白复合物，介导单向抑制。
