HCO3(-)-dependent alkalinizing transporter in adult rat ventricular myocytes: characterization and modulation.
The present work was designed to identify the HCO3(-)-dependent alkalinizing carrier in ventricular myocytes of normal and diabetic adult rats and to determine to what extent this system contributes to acid-equivalent extrusion after an intracellular acidification. We also examined the possible influence of intracellular Ca2+ (Cai2-) and glycolytic inhibition on the carrier activation. Intracellular pH (pHi) was recorded using seminaphthorhodafluor-1. The NH4+ method was used to induce an intracellular acid load. Evidence is provided for the existence of a Cl(-)-independent Na(+)-HCO3- cotransport contributing to pHi recovery from an intracellular acid load in ventricular cells of adult rats. Na(+)-HCO3- cotransport accounts for 33% of the total acid-equivalent efflux (JHe) from normal adult myocytes after intracellular acidification at pHi 6.75 in CO2/HCO3(-)-buffered solution. In addition, the activity of this carrier, which is not affected either by decreasing Cai2+ or by inhibiting Ca2+/calmodulin protein kinase II, is down-regulated by inhibition of glycolysis. Under pathophysiological conditions such as diabetes, although total JHe was significantly decreased compared with normal myocytes, JHe carried by Na(+)-HCO3- cotransport remained unchanged. However, because of a decrease in Na+/H+ exchange, the contribution of this carrier to total JHe increased with decreasing pHi (i.e., under conditions that may be associated with an ischemic episode), reaching approximately 58% of total JHe at pHi 6.75 (vs. approximately 33% in normal myocytes.
Le Prigent
K
K
Laboratoire de Physiologie Cellulaire, Université Paris XI, Orsay, France.
Lagadic-Gossmann
D
D
Mongodin
E
E
Feuvray
D
D
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002712:Chlorides / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006019:Glycolysis; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D006863:Hydrogen-Ion Concentration; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012964:Sodium / Q000494:pharmacology; D027982:Sodium-Bicarbonate Symporters
D001639:Bicarbonates; D002352:Carrier Proteins; D002712:Chlorides; D027982:Sodium-Bicarbonate Symporters; D000584:Amiloride; D003847:Deoxyglucose; D012964:Sodium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium