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The Na/K pump is a P-type ATPase that exchanges three intracellular Na(+) ions for two extracellular K(+) ions through the plasmalemma of nearly all animal cells. The mechanisms involved in cation selection by the pump's ion-binding sites (site I and site II bind either Na(+) or K(+); site III binds only Na(+)) are poorly understood. We studied cation selectivity by outward-facing sites (high K(+) affinity) of Na/K pumps expressed in Xenopus oocytes, under voltage clamp. Guanidinium(+), methylguanidinium(+), and aminoguanidinium(+) produced two phenomena possibly reflecting actions at site III: (i) voltage-dependent inhibition (VDI) of outwardly directed pump current at saturating K(+), and (ii) induction of pump-mediated, guanidinium-derivative-carried inward current at negative potentials without Na(+) and K(+). In contrast, formamidinium(+) and acetamidinium(+) induced K(+)-like outward currents. Measurement of ouabain-sensitive ATPase activity and radiolabeled cation uptake confirmed that these cations are external K(+) congeners. Molecular dynamics simulations indicate that bound organic cations induce minor distortion of the binding sites. Among tested metals, only Li(+) induced Na(+)-like VDI, whereas all metals tested except Na(+) induced K(+)-like outward currents. Pump-mediated K(+)-like organic cation transport challenges the concept of rigid structural models in which ion specificity at site I and site II arises from a precise and unique arrangement of coordinating ligands. Furthermore, actions by guanidinium(+) derivatives suggest that Na(+) binds to site III in a hydrated form and that the inward current observed without external Na(+) and K(+) represents cation transport when normal occlusion at sites I and II is impaired. These results provide insights on external ion selectivity at the three binding sites.
Bezanilla,
Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons.
1972, Pubmed
Bezanilla,
Negative conductance caused by entry of sodium and cesium ions into the potassium channels of squid axons.
1972,
Pubmed Cornelius,
Variable stoichiometry in reconstituted shark Na,K-ATPase engaged in uncoupled efflux.
1990,
Pubmed Forbush,
Rapid release of 42K or 86Rb from two distinct transport sites on the Na,K-pump in the presence of Pi or vanadate.
1987,
Pubmed Gadsby,
Steady-state current-voltage relationship of the Na/K pump in guinea pig ventricular myocytes.
1989,
Pubmed Gatto,
Cys(577) is a conformationally mobile residue in the ATP-binding domain of the Na,K-ATPase alpha-subunit.
1999,
Pubmed Gatto,
Similarities and differences between organic cation inhibition of the Na,K-ATPase and PMCA.
2006,
Pubmed Gatto,
Kinetic characterization of tetrapropylammonium inhibition reveals how ATP and Pi alter access to the Na+-K+-ATPase transport site.
2005,
Pubmed Hemsworth,
Electrogenic Li+/Li+ exchange mediated by the Na+-K+ pump in rabbit cardiac myocytes.
1997,
Pubmed Heyse,
Partial reactions of the Na,K-ATPase: determination of rate constants.
1994,
Pubmed Hille,
The hydration of sodium ions crossing the nerve membrane.
1971,
Pubmed Hille,
The permeability of the sodium channel to organic cations in myelinated nerve.
1971,
Pubmed Holmgren,
Three distinct and sequential steps in the release of sodium ions by the Na+/K+-ATPase.
2000,
Pubmed Li,
A third Na+-binding site in the sodium pump.
2005,
Pubmed
,
Xenbase Li,
The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current.
2006,
Pubmed
,
Xenbase Meier,
Hyperpolarization-activated inward leakage currents caused by deletion or mutation of carboxy-terminal tyrosines of the Na+/K+-ATPase {alpha} subunit.
2010,
Pubmed
,
Xenbase Noskov,
Importance of hydration and dynamics on the selectivity of the KcsA and NaK channels.
2007,
Pubmed Noskov,
Control of ion selectivity in LeuT: two Na+ binding sites with two different mechanisms.
2008,
Pubmed Ogawa,
Homology modeling of the cation binding sites of Na+K+-ATPase.
2002,
Pubmed Peluffo,
Effect of ADP on Na(+)-Na(+) exchange reaction kinetics of Na,K-ATPase.
2004,
Pubmed Post,
Activation by adenosine triphosphate in the phosphorylation kinetics of sodium and potassium ion transport adenosine triphosphatase.
1972,
Pubmed Poulsen,
Neurological disease mutations compromise a C-terminal ion pathway in the Na(+)/K(+)-ATPase.
2010,
Pubmed
,
Xenbase Rettinger,
Characteristics of Na+/K(+)-ATPase mediated proton current in Na(+)- and K(+)-free extracellular solutions. Indications for kinetic similarities between H+/K(+)-ATPase and Na+/K(+)-ATPase.
1996,
Pubmed
,
Xenbase Sachs,
The order of addition of sodium and release of potassium at the inside of the sodium pump of the human red cell.
1986,
Pubmed Shinoda,
Crystal structure of the sodium-potassium pump at 2.4 A resolution.
2009,
Pubmed Vasilyev,
Effect of extracellular pH on presteady-state and steady-state current mediated by the Na+/K+ pump.
2004,
Pubmed
,
Xenbase Wang,
A conformation of Na(+)-K+ pump is permeable to proton.
1995,
Pubmed
,
Xenbase Yaragatupalli,
Altered Na+ transport after an intracellular alpha-subunit deletion reveals strict external sequential release of Na+ from the Na/K pump.
2009,
Pubmed
,
Xenbase
