Na+-H+ antiporter in posthypercapnic state.
Posthypercapnic metabolic alkalosis has been attributed to decreased HCO3 excretion because of low glomerular filtration rate (GFR), volume contraction, or chloride depletion. We have previously shown that chronic hypercapnia enhances the Vmax of the Na+-H+ antiporter. We reasoned that an increased Vmax of the Na+-H+ antiporter could play a role in the maintenance of posthypercapnic metabolic alkalosis. To test this hypothesis, we measured the kinetics of the Na+-H+ antiporter by the dissipation of the quenching of acridine orange fluorescence in purified brush-border membrane obtained from posthypercapnic rabbits. The kinetic parameters were measured in controls and in rabbits that were exposed to hypercapnia for 48 h and then allowed to breathe room air for 3, 24, or 48 h. In luminal membranes prepared from posthypercapnic animals, the Vmax of the Na+-H+ antiporter was significantly increased after 3 and 24 h but not after 48 h compared with controls. The increase in Vmax was not different from that of hypercapnic animals. There was no difference in the Km of the Na+-H+ antiporter among these five groups. Amiloride inhibited the Vmax equally in membranes from control and posthypercapnic rabbits. Proton permeability was comparable among the groups. These data indicate that the increase in Vmax in posthypercapnic rabbits is mediated through the electroneutral Na+-H+ exchange and not through conductive H+ and Na+ pathway. Glucose uptake was not different in control and posthypercapnia, indicating a selective increase in Na+-H+ antiporter activity. At 3 and 24 h posthypercapnia, HCO3 concentration was higher than control.(ABSTRACT TRUNCATED AT 250 WORDS)
Yang
W C
WC
Department of Medicine, University of Illinois at Chicago.
Arruda
J A
JA
Talor
Z
Z
D000042:Absorption; D000136:Acid-Base Equilibrium; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D005919:Glomerular Filtration Rate; D005947:Glucose / Q000378:metabolism; D006935:Hypercapnia / Q000378:metabolism*; D007700:Kinetics; D010539:Permeability; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D001639:Bicarbonates; D002352:Carrier Proteins; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D005947:Glucose