DIDS and the Janus-faced Na~+-K~+-activated ATPase. Focus on 'DIDS inhibits Na-K-ATPase activity in porcine nonpigmented ciliary epithelial cells by a Src family kinase-dependent mechanism'

摘要

the maintenance of mammalian cell volume fundamentally rests on net cation extrusion through Na~+-K~+-activated ATPase, the Na~+ pump. The publication by Shahidullah et al. (11) persuasively identifies the series of events by which a widely used inhibitor of anion transport, DIDS, can reduce Na~+ pump activity of porcine nonpigmented ciliary epithelial (NPE) cells. DIDS sequentially acidifies the NPE cells and activates Src family kinases (SFK), thereby triggering phosphorylation and inhibition of Na~+-K~+-activated ATPase (Fig. 1). A pH dependence of pump activity has been long known; Na~+-K~+-ATPase activity of Xe-nopus membrane homogenates displays a pH maximum at ~pH 7 (10). The authors' results may be clinically relevant. By inhibiting Na~+ pump activity, DIDS can reduce porcine aqueous humor formation and thereby lower intraocular pressure. Reducing intraocular pressure remains the only documented approach for delaying the onset and slowing the progression of irreversible blindness in glaucoma. In addition to this potential clinical implication, the authors' observations are broadly instructive in two additional ways.