title: Extracellular allosteric Na(+) binding to the Na(+),K(+)-ATPase in cardiac myocytes.
abstract: Whole-cell patch-clamp measurements of the current, Ip, produced by the Na(+),K(+)-ATPase across the plasma membrane of rabbit cardiac myocytes show an increase in Ip over the extracellular Na(+) concentration range 0-50 mM. This is not predicted by the classical Albers-Post scheme of the Na(+),K(+)-ATPase mechanism, where extracellular Na(+) should act as a competitive inhibitor of extracellular K(+) binding, which is necessary for the stimulation of enzyme dephosphorylation and the pumping of K(+) ions into the cytoplasm. The increase in Ip is consistent with Na(+) binding to an extracellular allosteric site, independent of the ion transport sites, and an increase in turnover via an acceleration of the rate-determining release of K(+) to the cytoplasm, E2(K(+))2 → E1 + 2K(+). At normal physiological concentrations of extracellular Na(+) of 140 mM, it is to be expected that binding of Na(+) to the allosteric site would be nearly saturated. Its purpose would seem to be simply to optimize the enzyme's ion pumping rate under its normal physiological conditions. Based on published crystal structures, a possible location of the allosteric site is within a cleft between the α- and β-subunits of the enzyme.
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Sydney, Australia; Kolling Institute, University of Sydney, Sydney, Australia.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Garcia
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Sydney, Australia; Kolling Institute, University of Sydney, Sydney, Australia.
authors.forename: Natasha A S
authors.initials: NA
authors.lastname: Fry
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Sydney, Australia; Kolling Institute, University of Sydney, Sydney, Australia.
authors.forename: Keyvan
authors.initials: K
authors.lastname: Karimi
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Sydney, Australia; Kolling Institute, University of Sydney, Sydney, Australia.
authors.forename: Chia-chi
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Faculty of Biology, University of Konstanz, Konstanz, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Apell
authors.affiliation: Department of Cardiology, Royal North Shore Hospital, Sydney, Australia; Kolling Institute, University of Sydney, Sydney, Australia. Electronic address: helge.rasmussen@sydney.edu.au.
authors.forename: Helge H
authors.initials: HH
authors.lastname: Rasmussen
authors.affiliation: School of Chemistry, University of Sydney, Sydney, Australia. Electronic address: r.clarke@chem.usyd.edu.au.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Clarke
mesh_terms: D000200:Action Potentials; D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000378:metabolism*
chemical_list: D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium