title: A model of Na+/H+ exchanger and its central role in regulation of pH and Na+ in cardiac myocytes.
abstract: A new kinetic model of the Na(+)/H(+) exchanger (NHE) was developed by fitting a variety of major experimental findings, such as ion-dependencies, forward/reverse mode, and the turnover rate. The role of NHE in ion homeostasis was examined by implementing the NHE model in a minimum cell model including intracellular pH buffer, Na(+)/K(+) pump, background H(+), and Na(+) fluxes. This minimum cell model was validated by reconstructing recovery of pH(i) from acidification, accompanying transient increase in [Na(+)](i) due to NHE activity. Based on this cell model, steady-state relationships among pH(i), [Na(+)](I), and [Ca(2+)](i) were quantitatively determined, and thereby the critical level of acidosis for cell survival was predicted. The acidification reported during partial blockade of the Na(+)/K(+) pump was not attributed to a dissipation of the Na(+) gradient across the membrane, but to an increase in indirect H(+) production. This NHE model, though not adapted to the dimeric behavioral aspects of NHE, can provide a strong clue to quantitative prediction of degree of acidification and accompanying disturbance of ion homeostasis under various pathophysiological conditions.
authors.affiliation: Biosimulation Project, Faculty of Bioinformatics, Ritsumeikan University, Kusatsu, Japan.
authors.forename: Chae Young
authors.initials: CY
authors.lastname: Cha
authors.forename: Chiaki
authors.initials: C
authors.lastname: Oka
authors.forename: Yung E
authors.initials: YE
authors.lastname: Earm
authors.forename: Shigeo
authors.initials: S
authors.lastname: Wakabayashi
authors.forename: Akinori
authors.initials: A
authors.lastname: Noma
mesh_terms: D000138:Acidosis / Q000378:metabolism; D000465:Algorithms; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000502:physiology; D003198:Computer Simulation; D006706:Homeostasis / Q000502:physiology; D006859:Hydrogen / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D042541:Intracellular Space / Q000378:metabolism; D007477:Ions / Q000378:metabolism; D007700:Kinetics; D008955:Models, Cardiovascular; D032383:Myocytes, Cardiac / Q000502:physiology*; D011690:Purkinje Fibers / Q000502:physiology; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism*
chemical_list: D007477:Ions; D017923:Sodium-Hydrogen Exchangers; D006859:Hydrogen; D012964:Sodium