Na,K-ATPase: A murzyme facilitating thermodynamic equilibriums at the membrane-interface

The redox metabolic paradigm of murburn concept advocates that diffusible reactive species (DRS, particularly oxygen-centric radicals) are mainstays of physiology, and not mere pathological manifestations. The murburn purview of cellular function also integrates the essential principles of bioenergetics, thermogenesis, homeostasis, electrophysiology, and coherence. In this context, any enzyme that generates/modulates/utilizes/sustains DRS functionality is called a murzyme. We have demonstrated that several water-soluble (peroxidases, lactate dehydrogenase, hemogoblin, etc.) and membrane-embedded (Complexes I-V in mitochondria, Photosystems I/II in chloroplasts, rhodopsin/transducin in rod cells, etc.) proteins serve as murzymes. The membrane protein of Na,K-ATPase (NKA, also known as sodium-potassium pump) is the focus of this article, owing to its centrality in neuro-cardio-musculo electrophysiology. Herein, via a series of critical queries starting from the geometric/spatio-temporal considerations of diffusion/mass transfer of solutes in cells to an update on structural/distributional features of NKA in diverse cellular systems, and from various mechanistic aspects of ion-transport (thermodynamics, osmoregulation, evolutionary dictates, etc.) to assays/explanations of inhibitory principles like cardiotonic steroids (CTS), we first highlight some unresolved problems in the field. Thereafter, we propose and apply a minimalist murburn model of trans-membrane ion-differentiation by NKA to address the physiological inhibitory effects of trans-dermal peptide, lithium ion, volatile anesthetics, confirmed interfacial DRS + proton modulators like nitrophenolics and unsaturated fatty acid, and the diverse classes of molecules like CTS, arginine, oximes, etc. These explanations find a pan-systemic connectivity with the inhibitions/uncouplings of other membrane proteins in cells.