A model of Na+/H+ exchanger and its central role in regulation of pH and Na+ in cardiac myocytes.
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.
Cha
Chae Young
CY
Biosimulation Project, Faculty of Bioinformatics, Ritsumeikan University, Kusatsu, Japan.
Oka
Chiaki
C
Earm
Yung E
YE
Wakabayashi
Shigeo
S
Noma
Akinori
A
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*
D007477:Ions; D017923:Sodium-Hydrogen Exchangers; D006859:Hydrogen; D012964:Sodium