• Cholesterol depletion inhibits Na+,K+-ATPase activity in a near-native membrane environment 

      Garcia, Alvaro; Lev, Bogdan; Hossain, Khondker R.; Gorman, Amy; Diaz, Dil; Pham, T. H. Nguyen; Cornelius, Flemming; Allen, Toby W.; Clarke, Ronald J.
      Published 2019-02-15
      Cholesterol’s effects on Na+,K+-ATPase reconstituted in phospholipid vesicles have been extensively studied. However, previous studies have reported both cholesterol-mediated stimulation and inhibition of Na+,K+-ATPase ...
      Open Access
      Article
    • Effect of posttranslational modification on the Na+, K+ ATPase kinetics 

      Garcia, Alvaro
      Published 2014-08-29
      The Na+, K+ ATPase is an essential membrane protein in eukaryotic cells, which transports Na+ out of the cell in exchange for K+ into the cell. For this transport it hydrolyses one molecule of ATP for each cycle. The ...
      Open Access
      PhD Doctorate
    • Electrostatic stabilization plays a central role in autoinhibitory regulation of the Na+,K+-ATPase 

      Jiang, Qiucen; Garcia, Alvaro; Han, Minwoo; Cornelius, Flemming; Apell, Hans-Jurgen; Khandelia, Himanshu; Clarke, Ronald J.
      Published 2017-01-24
      The Na+,K+-ATPase is present in the plasma membrane of all animal cells. It plays a crucial role in maintaining the Na+ and K+ electrochemical potential gradients across the membrane, which are essential in numerous ...
      Open Access
      Article
    • Evidence for ATP interaction with phosphatidylcholine bilayers 

      Garcia, Alvaro; Pochinda, Simon; Elgaard-Jorgensen, Paninnguaq N.; Khandelia, Himanshu; Clarke, Ronald J.
      Published 2019-07-10
      ATP is a fundamental intracellular molecule and is thought to diffuse freely throughout the cytosol. Evidence obtained from nucleoside-sensing sarcolemmal ion channels and red blood cells, however, suggest that ATP is ...
      Open Access
      Article
    • Extracellular allosteric Na+ binding to the Na+,K+-ATPase in cardiac myocytes 

      Garcia, Alvaro; Fry, Natasha A. S.; Karimi, Keyvan; Liu, Chia-chi; Apell, Hans-Jurgen; Rasmussen, Helge H.; Clarke, Ronald J.
      Published 2013-12-01
      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. ...
      Open Access
      Article
    • Glutathionylation-dependence of N+-K+-pump currents can mimic reduced subsarcolemmal Na+ diffusion 

      Garcia, Alvaro; Liu, Chia-Chi; Cornelius, Flemming; Clarke, Ronald J.; Rasmussen, Helge H.
      Published 2016-03-01
      The existence of a subsarcolemmal space with restricted diffusion for Na+ in cardiac myocytes has been inferred from a transient peak electrogenic Na+-K+ pump current beyond steady state on re-exposure of myocytes to K+ ...
      Open Access
      Article
    • Identification of electric-field-dependent steps in the Na+,K+-pump cycle 

      Mares, Laura J.; Garcia, Alvaro; Rasmussen, Helge H.; Cornelius, Flemming; Mahmmoud, Yasser A.; Berlin, Joshua R.; Lev, Bogdan; Allen, Toby W.; Clarke, Ronald J.
      Published 2014-09-01
      The charge transporting activity of the Na+,K+-ATPase depends on its surrounding electric field. To isolate which steps of the enzyme’s reaction cycle involve charge movement we have investigated the response of the ...
      Open Access
      Article
    • Interaction of N-terminal peptide analogues of the Na+,K+-ATPase with membranes 

      Nguyen, Khoa; Garcia, Alvaro; Sani, Marc-Antoine; Diaz, Dil; Dubey, Vikas; Clayton, Daniel; Dal Poggetto, Giovanni; Cornelius, Flemming; Payne, Richard J.; Separovic, Frances; Khandelia, Himanshu; Clarke, Ronald J.
      Published 2018-03-06
      The Na+,K+-ATPase, which is present in the plasma membrane of all animal cells, plays a crucial role in maintaining the Na+ and K+ electrochemical potential gradients across the membrane. Recent studies have suggested that ...
      Open Access
      Article
    • Membrane accessibility of glutathione 

      Garcia, Alvaro; Eljack, Nasma D.; Sani, Marc-Antoine; Separovic, Frances; Rasmussen, Helge H.; Kopec, Wojciech; Khandelia, Himanshu; Cornelius, Flemming; Clarke, Ronald J.
      Published 2015-07-30
      Regulation of the ion pumping activity of the Na+,K+-ATPase is crucial to the survival of animal cells. Recent evidence has suggested that the activity of the enzyme could be controlled by glutathionylation of cysteine ...
      Open Access
      Article
    • Polar interactions play an important role in the energetics of the main phase transition of phosphatidylcholine membranes 

      Garcia, Alvaro; Zou, Haipei; Hossain, Khondker R.; Xu, Qikui Henry; Buda, Annabelle; Clarke, Ronald J.
      Published 2019-01-08
      Conformational changes of membrane proteins are accompanied by deformation in the surrounding lipid bilayer. To gain insight into the energetics of membrane deformation, the phase behavior of dimyristoylphosphatidylcholine ...
      Open Access
      Article
    • Redox-dependent regulation of the Na+-K+ pump: New twists to an old target for treatment of heart failure 

      Liu, Chia-Chi; Fry, Natasha A. S.; Hamilton, Elisha J.; Chia, Karin K. M.; Garcia, Alvaro; Galougahi, Keyvan K.; Figtree, Gemma A.; Clarke, Ronald J.; Bundgaard, Henning; Rasmussen, Helge H.
      Published 2013-05-30
      By the time it was appreciated that the positive inotropic effect of cardiac glycosides is due to inhibition of the membrane Na+-K+ pump, glycosides had been used for treatment of heart failure on an empiric basis for ~200 ...
      Open Access
      Article
    • Stimulation of Na+,K+-ATPase activity as a possible driving foce in cholesterol evolution 

      Lambropoulos, Nicholas; Garcia, Alvaro; Clarke, Ronald J.
      Published 2015-12-29
      Cholesterol is exclusively produced by animals and is present in the plasma membrane of all animal cells. In contrast, the membranes of fungi and plants contain other sterols. To explain the exclusive preference of animal ...
      Open Access
      Article
    • The voltage-sensitive dye RH421 detects a Na+,K+-ATPase conformational change at the membrane interface 

      Garcia, Alvaro; Promod, Pratap R.; Lupfert, Christian; Cornelius, Flemming; Jacquemin, Denis; Lev, Bogdan; Allen, Toby W.; Clarke, Ronald J.
      Published 2017-01-20
      RH421 is a voltage-sensitive fluorescent styrylpyridinium dye which has often been used to probe the kinetics of Na+,K+-ATPase partial reactions. The origin of the dye’s response has up to now been unclear. Here we show ...
      Open Access
      Article