Involvement of anion exchange in the hypoxia/reoxygenation-induced changes in pHi and [Ca2+]i in cardiac myocyte

Abstract 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.