Cooper G J, Boron W F
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Am J Physiol. 1998 Dec;275(6):C1481-6. doi: 10.1152/ajpcell.1998.275.6.C1481.
A recent study on Xenopus oocytes [N. L. Nakhoul, M. F. Romero, B. A. Davis, and W. F. Boron. Am. J. Physiol. 274 (Cell Physiol. 43): C543-548, 1998] injected with carbonic anhydrase showed that expressing aquaporin 1 (AQP1) increases by approximately 40% the rate at which exposing the cell to CO2 causes intracellular pH to fall. This observation is consistent with several interpretations. Overexpressing AQP1 might increase apparent CO2 permeability by 1) allowing CO2 to pass through AQP1, 2) stimulating injected carbonic anhydrase, 3) enhancing the CO2 solubility of the membrane's lipid, or 4) increasing the expression of a native "gas channel." The purpose of the present study was to distinguish among these possibilities. We found that expressing the H2O channel AQP1 in Xenopus oocytes increases the CO2 permeability of oocytes in an expression-dependent fashion, whereas expressing the K+ channel ROMK1 has no effect. The mercury derivative p-chloromercuriphenylsulfonic acid (PCMBS), which inhibits the H2O movement through AQP1, also blocks the AQP1-dependent increase in CO2 permeability. The mercury-insensitive C189S mutant of AQP1 increases the CO2 permeability of the oocyte to the same extent as does the wild-type channel. However, the C189S-dependent increase in CO2 permeability is unaffected by treatment with PCMBS. These data rule out options 2-4 listed above. Thus our results suggest that CO2 passes through the pore of AQP1 and are the first data to demonstrate that a gas can enter a cell by a means other than diffusing through the membrane lipid.
最近一项针对非洲爪蟾卵母细胞的研究[N. L. 纳胡尔、M. F. 罗梅罗、B. A. 戴维斯和W. F. 博龙。《美国生理学杂志》274卷（细胞生理学43）：C543 - 548，1998年]表明，向卵母细胞注射碳酸酐酶后，表达水通道蛋白1（AQP1）会使细胞暴露于二氧化碳时细胞内pH下降的速率提高约40%。这一观察结果与几种解释相符。过表达AQP1可能通过以下方式增加表观二氧化碳通透性：1）使二氧化碳通过AQP1；2）刺激注射的碳酸酐酶；3）提高膜脂质的二氧化碳溶解度；4）增加天然“气体通道”的表达。本研究的目的是区分这些可能性。我们发现，在非洲爪蟾卵母细胞中表达水通道H2O通道AQP1会以一种依赖于表达量的方式增加卵母细胞的二氧化碳通透性，而表达钾通道ROMK1则没有影响。抑制水通过AQP1移动的汞衍生物对氯汞苯磺酸（PCMBS）也会阻断AQP1依赖的二氧化碳通透性增加。AQP1的汞不敏感C189S突变体使卵母细胞的二氧化碳通透性增加到与野生型通道相同的程度。然而，PCMBS处理对C189S依赖的二氧化碳通透性增加没有影响。这些数据排除了上述选项2 - 4。因此，我们的结果表明二氧化碳通过AQP1的孔道，并且是首批证明气体可以通过除扩散穿过膜脂质之外的方式进入细胞的数据。
