Carraro-Lacroix L R, Lessa L M A, Fernandez R, Malnic G
Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP, Brasil.
Braz J Med Biol Res. 2009 Feb;42(2):155-63. doi: 10.1590/s0100-879x2009000200002.
Vacuolar H+-ATPase is a large multi-subunit protein that mediates ATP-driven vectorial H+ transport across the membranes. It is widely distributed and present in virtually all eukaryotic cells in intracellular membranes or in the plasma membrane of specialized cells. In subcellular organelles, ATPase is responsible for the acidification of the vesicular interior, which requires an intraorganellar acidic pH to maintain optimal enzyme activity. Control of vacuolar H+-ATPase depends on the potential difference across the membrane in which the proton ATPase is inserted. Since the transport performed by H+-ATPase is electrogenic, translocation of H+-ions across the membranes by the pump creates a lumen-positive voltage in the absence of a neutralizing current, generating an electrochemical potential gradient that limits the activity of H+-ATPase. In many intracellular organelles and cell plasma membranes, this potential difference established by the ATPase gradient is normally dissipated by a parallel and passive Cl- movement, which provides an electric shunt compensating for the positive charge transferred by the pump. The underlying mechanisms for the differences in the requirement for chloride by different tissues have not yet been adequately identified, and there is still some controversy as to the molecular identity of the associated Cl--conducting proteins. Several candidates have been identified: the ClC family members, which may or may not mediate nCl-/H+ exchange, and the cystic fibrosis transmembrane conductance regulator. In this review, we discuss some tissues where the association between H+-ATPase and chloride channels has been demonstrated and plays a relevant physiologic role.
液泡H⁺-ATP酶是一种大型多亚基蛋白，介导ATP驱动的跨膜矢量H⁺转运。它广泛分布于几乎所有真核细胞的内膜或特化细胞的质膜中。在亚细胞器中，ATP酶负责使囊泡内部酸化，这需要细胞器内的酸性pH值来维持最佳酶活性。液泡H⁺-ATP酶的调控取决于质子ATP酶所插入膜的电位差。由于H⁺-ATP酶所进行的转运是生电的，在没有中和电流的情况下，泵使H⁺离子跨膜转运产生管腔正电压，产生一个限制H⁺-ATP酶活性的电化学势梯度。在许多细胞内细胞器和细胞质膜中，由ATP酶梯度建立的这种电位差通常通过平行且被动的Cl⁻移动而消散，Cl⁻移动提供了一个电分流，以补偿泵转移的正电荷。不同组织对氯离子需求差异的潜在机制尚未得到充分确定，并且关于相关Cl⁻传导蛋白的分子身份仍存在一些争议。已经鉴定出几种候选蛋白：ClC家族成员，其可能介导也可能不介导nCl⁻/H⁺交换，以及囊性纤维化跨膜传导调节因子。在这篇综述中，我们讨论了一些已证明H⁺-ATP酶与氯离子通道之间存在关联并发挥相关生理作用的组织。
