Increased tolerance to oxygen and glucose deprivation in astrocytes from Na+/H+ exchanger isoform 1 null mice

The ubiquitously expressed Na+/H+ exchanger isoform 1 (NHE1) functions as a major intracellular pH (pHi) regulatory mechanism in many cell types, and in some tissues its activity may contribute to ischemic injury. In the present study, cortical astrocyte cultures from wild-type (NHE1+/+) and NHE1-deficient (NHE1−/−) mice were used to investigate the role of NHE1 in pHi recovery and ischemic injury in astrocytes. In the absence of HCO3−, the mean resting pHi levels were 6.86 ± 0.03 in NHE1+/+ astrocytes and 6.53 ± 0.04 in NHE1−/− astrocytes. Removal of extracellular Na+ or blocking of NHE1 activity by the potent NHE1 inhibitor HOE-642 significantly reduced the resting level of pHi in NHE1+/+ astrocytes. NHE1+/+ astrocytes exhibited a rapid pHi recovery (0.33 ± 0.08 pH unit/min) after NH4Cl prepulse acid load. The pHi recovery in NHE1+/+ astrocytes was reversibly inhibited by HOE-642 or removal of extracellular Na+. In NHE1−/− astrocytes, the pHi recovery after acidification was impaired and not affected by...