Involvement of anion exchange in the hypoxia/reoxygenation-induced changesin pH(i) and [Ca2+](i) in cardiac myocyte

The involvement of Cl-/HCO3- exchange in hypoxia/reoxygenation-induced chan ges in pH(i) and Ca2+ concentration ([Ca2+](i)) was examined in rat ventric ular myocytes. During 10-min hypoxia. the initial pH(i) (7.21 +/- 0.04) fel l to below 6.8. Subsequent reperfusion with reoxygenated buffer returned th is acidic pH(i) to the neutral range with increases in [Ca2+](i). These res ponses were reduced by the removal of Cl- or HCO3- and by the addition of a nion exchange inhibitors, SITS (4-acetamido-4' isothiocyanato-stilbene-2,2' -disulfonic acid) and DIDS (4.4'-diisothiocyano-stilbene-2,2'-disulfonic ac id). while inhibitors for the Cl- channel and Na+/K+/2Cl(-) cotransport wer e without effects. The hypoxia-induced acidification was attenuated by prot ein kinase C inhibitors. calphostin C and chelerythrine. but not by a prote in kinase A inhibitor. KT5720. Under normoxic condition, protein kinase C a ctivation induced a SITS-sensitive acidification. Furthermore, in electrica lly driven rat papillary muscle, SITS and DIDS improved the recovery of dev eloped tension during the reoxygenation. These results suggest that the hyp oxia-induced decrease in pHi is mediated at least in part by anion exchange stimulation through protein kinase C activation, and this exchange takes p art in the reoxygenation-induced Ca2+ overload as well as contractile dysfu nction. (C) 2001 Elsevier Science B.V. All rights reserved.