Contribution of calcium ions to P2X channel responses
Contribution of calcium ions to P2X channel responses
复制标题
DOI：
10.1523/jneurosci.5429-03.2004
复制
发表时间：
2004-03-31
影响因子：
5.3
通讯作者：
Khakh, BS
中科院分区：
文献类型：
--
作者：
Egan, TM;Khakh, BS
Ca 2+通过递质门控阳离子通道（包括ATP门控P2 X通道）进入，有助于可兴奋和不可兴奋细胞中的一系列生理过程，但流经P2 X通道的Ca 2+的绝对量尚不清楚。在这里，我们解决的问题，到底有多少Ca 2+流通过P2 X通道和报告的发现，ATP门控P2 X通道家族有显着高的Ca 2+通量相比，其他通道的发射机乙酰胆碱，5-羟色胺，质子，谷氨酸。几个同源和异源P2 X通道显示相当于NMDA通道的部分Ca 2+电流，迄今为止，这一直被认为是最大的来源，transmitter激活的Ca 2+通量。我们进一步表明，NMDA和P2 X通道可能使用不同的机制，以促进跨膜Ca 2+通量。我们发现，突变三个关键的极性氨基酸降低了P2 X（2）受体的Ca 2+通量，这表明这些残基聚集在孔内形成一种新型的Ca 2+选择性区域。总体而言，我们的数据确定P2 X通道作为一个大的来源，在静息膜电位的递质激活的Ca 2+内流和支持的假设，极性氨基酸有助于在ATP门控离子通道中的Ca 2+选择。
Ca2+ entry through transmitter-gated cation channels, including ATP-gated P2X channels, contributes to an array of physiological processes in excitable and non-excitable cells, but the absolute amount of Ca2+ flowing through P2X channels is unknown. Here we address the issue of precisely how much Ca2+ flows through P2X channels and report the finding that the ATP-gated P2X channel family has remarkably high Ca2+ flux compared with other channels gated by the transmitters ACh, serotonin, protons, and glutamate. Several homomeric and heteromeric P2X channels display fractional Ca2+ currents equivalent to NMDA channels, which hitherto have been thought of as the largest source of transmitter-activated Ca2+ flux. We further suggest that NMDA and P2X channels may use different mechanisms to promote Ca2+ flux across membranes. We find that mutating three critical polar amino acids decreases the Ca2+ flux of P2X(2) receptors, suggesting that these residues cluster to form a novel type of Ca2+ selectivity region within the pore. Overall, our data identify P2X channels as a large source of transmitter-activated Ca2+ influx at resting membrane potentials and support the hypothesis that polar amino acids contribute to Ca2+ selection in an ATP-gated ion channel.