Pasternack Richard A, Quade Bianca N, Marshall Aniko, Parker Mark D
Department of Physiology and Biophysics, The State University of New York: The University at Buffalo, Buffalo, NY, United States.
Department of Ophthalmology, The State University of New York: The University at Buffalo, Buffalo, NY, United States.
Front Physiol. 2024 Aug 14;15:1440720. doi: 10.3389/fphys.2024.1440720. eCollection 2024.
SLC4A11 is the most abundant membrane transport protein in corneal endothelial cells. Its functional presence is necessary to support the endothelial fluid pump that draws fluid from the corneal stroma, preventing corneal edema. Several molecular actions have been proposed for SLC4A11 including HO transport and cell adhesion. One of the most reproduced actions that SLC4A11 mediates is a H (or OH) conductance that is enhanced in the presence of NHCl. The mechanism by which this occurs is controversial with some providing evidence in favor of NH-H cotransport and others providing evidence for uncoupled H transport that is indirectly stimulated by the effects of NHCl upon intracellular pH and membrane potential. In the present study we provide new evidence and revisit previous studies, to support a model in which NHCl causes direct allosteric activation of SLC4A11 by means of an acidic shift in the intracellular pK (pK) that governs the relationship between intracellular pH (pH) and SLC4A11 H-conductance. These findings have important implications for the assignment of a physiological role for SLC4A11.
溶质载体家族4成员11（SLC4A11）是角膜内皮细胞中含量最丰富的膜转运蛋白。其功能性存在对于维持从角膜基质抽吸液体的内皮液体泵至关重要，可预防角膜水肿。关于SLC4A11已经提出了几种分子作用，包括碳酸氢根离子（HCO₃⁻）转运和细胞黏附。SLC4A11介导的最具重复性的作用之一是在氯化铵（NH₄Cl）存在下增强的氢离子（H⁺）（或氢氧根离子，OH⁻）电导。其发生机制存在争议，一些人提供了支持铵离子（NH₄⁺）-氢离子（H⁺）共转运的证据，而另一些人则提供了非偶联氢离子（H⁺）转运的证据，这种转运是由氯化铵（NH₄Cl）对细胞内pH值和膜电位的影响间接刺激的。在本研究中，我们提供了新的证据并重新审视了先前的研究，以支持一个模型，即氯化铵（NH₄Cl）通过控制细胞内pH值（pHi）与SLC4A11氢离子（H⁺）电导之间关系的细胞内解离常数（pK）的酸性偏移，引起SLC4A11的直接变构激活。这些发现对确定SLC4A11的生理作用具有重要意义。
