Disease mutations of human α3 Na⁺/K⁺-ATPase define extracellular Na⁺ binding/occlusion kinetics at ion binding site III.

ABSTRACT: Na⁺/K⁺-ATPase, which creates transmembrane electrochemical gradients by exchanging 3 Na⁺ for 2 K⁺, is central to the pathogenesis of neurological diseases such as alternating hemiplegia of childhood. Although Na⁺/K⁺-ATPase has 3 distinct ion binding sites I-III, the difficulty of distinguishing ion binding events at each site from the others hinders kinetic study of these transitions. Here, we show that binding of Na⁺ at each site in the human α3 Na⁺/K⁺-ATPase can be resolved using extracellular Na⁺-mediated transient currents. When Na⁺/K⁺-ATPase is constrained to bind and release only Na⁺, three kinetic components: fast, medium, and slow, can be is

SUBMITTER: Moreno C 

PROVIDER: S-EPMC9585393 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature