Na+/Ca2+ exchanger activity induces a slow DC potential after in vitro ischemia in rat hippocampal CA1 region.

Abstract In rat hippocampal CA1 neurons recorded intracellularly from tissue slices, a rapid depolarization occurred ≈5 min after application of ischemia-simulating medium. In extracellular recordings obtained from CA1 region, a rapid negative-going DC potential (rapid DC potential) was recorded, corresponding to a rapid depolarization. When oxygen and glucose were reintroduced after generating the rapid depolarization, the membrane further depolarized and the potential became 0 mV after 5 min. Contrary, the DC potential began to repolarize slowly and subsequently a slow negative-going DC potential (slow DC potential) occurred within 1 min. A prolonged application of ischemia-simulating medium suppressed the slow DC potential. Addition of a high concentration of ouabain in normoxic medium reproduced a rapid but not a slow DC potential. The slow DC potential was reduced in low Na + - or Co 2+ -containing medium, but was not affected in low Cl − , high K + or K + -free medium, suggesting that the slow DC potential is Na + -and Ca 2+ -dependent. Ni 2+ (Ca 2+ channel blocker as well as the Na + /Ca 2+ exchanger blocker) and benzamil hydrochloride (Na + /Ca 2+ exchanger blocker) reduced the slow DC potential dose-dependently. These results suggest that the slow DC potential is mediated by forward mode operation of Na + /Ca 2+ exchangers in non-neuronal cells, and that reactivation of Na + , K + -ATPase is necessary to the Na + /Ca 2+ exchanger activity.