Na+-H+ exchange and pH regulation in red blood cells: role of uncatalyzed H2CO3 dehydration.
Erythrocytes of rainbow trout respond to adrenergic stimulation by activation of a Na+-H+ exchange. When red blood cells are suspended in their own plasma and equilibrated with a convenient gas mixture in a tonometer, the extrusion of H+ induces a fast, very strong acidification of the blood (by 0.5-0.7 pH units), explained as follows. Excretion of H+ into a medium containing HCO3- causes the formation of H2CO3. The uncatalyzed dehydration of H2CO3 is slow so that H+ accumulates above the level that would prevail at equilibrium, promoting a strong acid disequilibrium pH. Then the blood pH progressively returns to a value close to its initial value because of the slow uncatalyzed dehydration of H2CO3 and washout of the CO2 so produced. The period of acid disequilibrium pH, however, is lengthened because part of the CO2 generated by the spontaneous dehydration is not washed out by tonometry but diffuses into the red cells where it is rapidly converted into HCO3- and H+ by carbonic anhydrase and then excreted by Na+-H+ and Cl-HCO3- exchangers. This recycling process "refuels" the ionic reaction, increasing the time needed to reach equilibrium. The anion exchanger does not sense this strong acid disequilibrium pH, since the external HCO3- concentration is practically unchanged at that time. During the extracellular pH (pHe) recovery period, simultaneously extracellular HCO3- content decreases and intracellular Cl- content increases. Thus intracellular pH and pHe appear to be uncoupled. This overall interpretation is confirmed by experiments using carbonic anhydrase and drugs such as propranolol and amiloride.(ABSTRACT TRUNCATED AT 250 WORDS)
Motais
R
R
Départment de Biologie du Commissariat à l'Energie Atomique, Laboratoire Jean Maetz, Villefranche-sur-Mer, France.
Fievet
B
B
Garcia-Romeu
F
F
Thomas
S
S
D000136:Acid-Base Equilibrium; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000097:blood; D002245:Carbon Dioxide / Q000097:blood; D002254:Carbonates / Q000097:blood*; D002255:Carbonic Acid / Q000097:blood*; D002256:Carbonic Anhydrases / Q000097:blood / Q000494:pharmacology; D002352:Carrier Proteins / Q000097:blood; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D011433:Propranolol / Q000494:pharmacology; D011522:Protons; D012487:Salmonidae / Q000097:blood*; D012964:Sodium / Q000097:blood*; D017923:Sodium-Hydrogen Exchangers; D014337:Trout / Q000097:blood*
D001639:Bicarbonates; D002254:Carbonates; D002352:Carrier Proteins; D011522:Protons; D017923:Sodium-Hydrogen Exchangers; D002245:Carbon Dioxide; D002255:Carbonic Acid; D000584:Amiloride; D012964:Sodium; D011433:Propranolol; D002256:Carbonic Anhydrases; D007545:Isoproterenol