Involvement of anion exchange in the hypoxia/reoxygenation-induced changes in pH(i) and.
The involvement of Cl(-)/HCO(3)(-) exchange in hypoxia/reoxygenation-induced changes in pH(i) and Ca(2+) concentration ([Ca(2+)](i)) was examined in rat ventricular myocytes. During 10-min hypoxia, the initial pH(i) (7.21+/-0.04) fell to below 6.8. Subsequent reperfusion with reoxygenated buffer returned this acidic pH(i) to the neutral range with increases in [Ca(2+)](i). These responses were reduced by the removal of Cl(-) or HCO(3)(-) and by the addition of anion exchange inhibitors, SITS (4-acetamido-4'isothiocyanato-stilbene-2,2'disulfonic acid) and DIDS (4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid), while inhibitors for the Cl(-) channel and Na(+)/K(+)/2Cl(-) cotransport were without effects. The hypoxia-induced acidification was attenuated by protein kinase C inhibitors, calphostin C and chelerythrine, but not by a protein kinase A inhibitor, KT5720. Under normoxic condition, protein kinase C activation induced a SITS-sensitive acidification. Furthermore, in electrically driven rat papillary muscle, SITS and DIDS improved the recovery of developed tension during the reoxygenation. These results suggest that the hypoxia-induced decrease in pH(i) is mediated at least in part by anion exchange stimulation through protein kinase C activation, and this exchange takes part in the reoxygenation-induced Ca(2+) overload as well as contractile dysfunction.
Kawasaki
H
H
Department of Pharmacology, Kansai Medical University, 10-15 Fumizono-cho, Osaka 570-8506, Moriguchi, Japan.
Otani
H
H
Mishima
K
K
Imamura
H
H
Inagaki
C
C
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000818:Animals; D000838:Anions / Q000378:metabolism*; D001639:Bicarbonates / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002227:Carbazoles; D002478:Cells, Cultured; D002712:Chlorides / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000838:Anions; D001639:Bicarbonates; D002227:Carbazoles; D002712:Chlorides; D004791:Enzyme Inhibitors; D007211:Indoles; D009281:Naphthalenes; D011758:Pyrroles; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; C057416:KT 5720; D011493:Protein Kinase C; C058819:calphostin C; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D010100:Oxygen; D002118:Calcium