Alterations of K+ transport by the alpha 1 Na(+)-K+ pump in red blood cells of the Dahl salt-sensitive rat.
We studied the kinetic properties of the Na(+)-K+ pump in rat red blood cells (RBCs) of the Dahl salt-sensitive (DS) and salt-resistant (DR) strains by measuring unidirectional ouabain-sensitive (OS) Na+ and K+ fluxes (mmol/L cell x h = FU, mean +/- SE) and varying internal (i) and external (o) Na+ and K+ concentrations. OS Na+ efflux into Nao 140 mM, Ko 5 mM was similar in both strains in fresh cells as well as for Vmax and Km for Nai. However, DS pumps have significantly lower K+ influx than DR pumps in fresh cells, thereby giving rise to a higher Na:K coupling ratio. The lower rates of K+ influx were caused by a defective activation by Nai and Nao that led to significantly lower Vmax than in DR pumps. The activation of K+ influx by Ko in the presence of 140 mM Nao had a lower Vmax and a higher affinity in DS (Vmax 2.58 +/- 0.09 FU, n = 17, Km 0.63 +/- 0.23 mM) than in DR rats (Vmax 4.7 +/- 0.3 FU, n = 16; Km 1.9 +/- 0.2 mM). However, when Nao was removed, these two kinetic parameters became similar in both strains. OS 86Rb/K efflux from fresh RBCs was significantly higher in DS than in DR rats, because the K50 from Nai inhibition was threefold higher in DS pumps. In summary, the low rates of unidirectional and net K+ influx in DS cells are caused by impaired Nai and Nao activation as well as the high values of K+ efflux are caused by low affinity for Nai inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)
Romero
J R
JR
Endocrine-Hypertension Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Canessa
M
M
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology*; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000097:blood*; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood*
D010042:Ouabain; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium