Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, USA.
J Neurosci. 2011 Nov 16;31(46):16716-30. doi: 10.1523/JNEUROSCI.3362-11.2011.
ATP-gated ionotropic P2X2 receptors are widely expressed in neurons. Although the electrophysiological properties of P2X2 receptors have been extensively studied, little is known about the plasma membrane lateral mobility of P2X2 receptors or whether receptor mobility is regulated by ATP. Here we used single-molecule imaging with simultaneous whole-cell voltage-clamp recordings to track quantum dot-labeled P2X2 receptors in the dendrites of rat hippocampal neurons to explore P2X2 receptor mobility and its regulation. We find that plasma membrane P2X2 receptor lateral mobility in dendrites is heterogeneous but mostly Brownian in nature, consisting of mobile and slowly mobile receptor pools. Moreover, lateral mobility is P2X2 subunit and cell specific, is increased in an activation-dependent manner, and is regulated by cytosolic VILIP1, a calcium binding protein. Our data provide the first direct measures of P2X receptor mobility and show that P2X2 receptors are mobile ATP sensors, sampling more of the dendritic plasma membrane in response to ATP.
ATP 门控离子型 P2X2 受体广泛表达于神经元中。尽管 P2X2 受体的电生理特性已得到广泛研究，但对于 P2X2 受体的质膜侧向流动性或受体流动性是否受 ATP 调节知之甚少。在此，我们使用单分子成像与全细胞膜片钳记录同步，追踪量子点标记的大鼠海马神经元树突中的 P2X2 受体，以探索 P2X2 受体的流动性及其调节。我们发现树突中质膜 P2X2 受体的侧向流动性具有异质性，但主要呈布朗运动性质，由可动和慢动受体池组成。此外，侧向流动性具有 P2X2 亚基和细胞特异性，以激活依赖性方式增加，并受细胞质 VILIP1（一种钙结合蛋白）调节。我们的数据提供了 P2X 受体流动性的首次直接测量结果，并表明 P2X2 受体是可移动的 ATP 传感器，在响应 ATP 时可更多地采样树突质膜。
