Evolutionary adaptation of the sensitivity of connexin26 hemichannels to CO2.
Evolutionary adaptation of the sensitivity of connexin26 hemichannels to CO2.
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DOI：
10.1098/rspb.2016.2723
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发表时间：
2017-02-08
期刊：
影响因子：
--
通讯作者：
Dale N
中科院分区：
文献类型：
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作者：
de Wolf E;Cook J;Dale N
CO2很容易与H2O结合形成H2O和H+。由于血液中H+浓度仅增加100 nM（pH值降低0.1单位）即可证明是致命的，因此呼吸期间CO2的调节排泄是维持生命的重要过程。在啮齿动物和人类中，这一重要过程部分是通过连接蛋白26（Cx26）直接感知CO2来介导的。CO2与Cx26的半通道结合，导致它们打开并释放神经递质ATP。如果Cx26是所有恒温动物的一个通用的和重要的CO2传感器，那么一个简单的假设将证明，它应该表现出进化适应的动物与不同的稳态设定点调节动脉CO2分压（PaCO2）。在人类和大鼠中，PaCO2被调节在40 mmHg的设定点附近。相比之下，鸟类能够在低得多的PaCO2水平下维持脑血流和呼吸。化石哺乳动物，如鼹鼠，只生活在地下的洞穴中，既缺氧又高碳酸，并能在非常高碳酸的条件下茁壮成长。因此，我们比较了人类、鸡、大鼠和鼹鼠（Heterocephalus glaber）的Cx26对CO2的敏感性。我们发现，这两个亲和力和CO2结合Cx26的协同性已受到进化适应的方式与这四个物种的稳态要求一致。这类似于血红蛋白对整个动物王国的O2运输需求的进化适应，并支持Cx26是恒温动物中重要且通用的CO2传感器的假设。
CO2 readily combines with H2O to form and H+. Because an increase of only 100 nM in the concentration of H+ (a decrease of 0.1 unit of pH) in blood can prove fatal, the regulated excretion of CO2 during breathing is an essential life-preserving process. In rodents and humans, this vital process is mediated in part via the direct sensing of CO2 via connexin26 (Cx26). CO2 binds to hemichannels of Cx26 causing them to open and allow release of the neurotransmitter ATP. If Cx26 were to be a universal and important CO2 sensor across all homeothermic animals, then a simple hypothesis would posit that it should exhibit evolutionary adaptation in animals with different homeostatic set points for the regulation of partial pressure of arterial CO2 (PaCO2). In humans and rats, PaCO2 is regulated around a set point of 40 mmHg. By contrast, birds are able to maintain cerebral blood flow and breathing at much lower levels of PaCO2. Fossorial mammals, such as the mole rat, live exclusively underground in burrows that are both hypoxic and hypercapnic and can thrive under very hypercapnic conditions. We have therefore compared the CO2 sensitivity of Cx26 from human, chicken, rat and mole rat (Heterocephalus glaber). We find that both the affinity and cooperativity of CO2 binding to Cx26 have been subjected to evolutionary adaption in a manner consistent with the homeostatic requirements of these four species. This is analogous to the evolutionary adaptation of haemoglobin to the needs of O2 transport across the animal kingdom and supports the hypothesis that Cx26 is an important and universal CO2 sensor in homeotherms.