Regulation of the cytosolic pH set point for activation of the Na+/H+ antiport in human platelets: the roles of the Na+/Ca2+ exchange, the Na(+)-K(+)-2Cl- cotransport and cellular volume.
To explore further the mechanisms that regulate the Na+/H+ antiport in human platelets, we examined the effect of Na+ pump inhibition by ouabain and K+ removal from the extracellular medium on parameters of this transport system. Treatment with ouabain resulted in increased cytosolic free Ca2+ and Na+, coupled with an alkaline shift in the cytosolic pH set point for the Na+/H+ antiport. Inhibition of the Na+ pump by the removal of K+ from the medium increased the cytosolic Na+ but not the cytosolic Ca2+; yet this treatment also produced a substantial alkaline shift in the cytosolic pH set point for the Na+/H+ antiport. This effect appeared to relate to a decline in cellular volume and it was attenuated by the Na(+)-K(+)-2 Cl- cotransport inhibitor, bumetanide. These findings indicate: (a) a link between the Na+ pump and the Na+/H+ antiport, mediated by the Na+/Ca2+ exchange and the cytosolic free Ca2+, and (b) a link between the Na+/H+ antiport and the Na(+)-K(+)-2Cl- cotransport through cellular volume.
Kimura
M
M
Hypertension Research Center, University of Medicine and Dentistry of NJ-NJ Medical School, Newark 07103-2714.
Aviv
A
A
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D002352:Carrier Proteins / Q000097:blood*; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010042:Ouabain / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012964:Sodium / Q000097:blood; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D028021:Sodium-Potassium-Chloride Symporters; D002034:Bumetanide; D010042:Ouabain; D011189:Potassium Chloride; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium