The ERK pathway regulates Na(+)-HCO(3)(-) cotransport activity in adult rat cardiomyocytes.
The sarcolemmal Na(+)-HCO cotransporter (NBC) is stimulated by intracellular acidification and acts as an acid extruder. We examined the role of the ERK pathway of the MAPK cascade as a potential mediator of NBC activation by intracellular acidification in the presence and absence of angiotensin II (ANG II) in adult rat ventricular myocytes. Intracellular pH (pH(i)) was recorded with the use of seminaphthorhodafluor-1. The NH method was used to induce an intracellular acid load. NBC activation was significantly decreased with the ERK inhibitors PD-98059 and U-0126. NBC activity after acidification was increased in the presence of ANG II (pH(i) range of 6.75-7.00). ANG II plus PD-123319 (AT(2) antagonist) still increased NBC activity, whereas ANG II plus losartan (AT(1) antagonist) did not affect it. ERK phosphorylation (measured by immunoblot analysis) during intracellular acidification was increased by ANG II, an effect that was abolished by losartan and U-0126. In conclusion, the MAPK(ERK)-dependent pathway facilitates the rate of pH(i) recovery from acid load through NBC activity and is involved in the AT(1) receptor-mediated stimulation of such activity by ANG II.
Baetz
Delphine
D
Laboratoire de Physiologie Cellulaire and Centre National de la Recherche Scientifique, Hôpital Marie Lannelongue-Université Paris XI, 91405 Orsay Cedex, France.
Haworth
Robert S
RS
Avkiran
Metin
M
Feuvray
Danielle
D
D000143:Acids / Q000378:metabolism; D000367:Age Factors; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D006352:Heart Ventricles / Q000166:cytology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000378:metabolism; D012508:Sarcolemma / Q000201:enzymology; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000143:Acids; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D027982:Sodium-Bicarbonate Symporters; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D020928:Mitogen-Activated Protein Kinases