Role of Na+-K+-Cl− cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia
2007
Na+-K+-Cl− cotransporter isoform 1 (NKCC1) and reverse mode operation of the Na+/Ca2+ exchanger (NCX) contribute to intracellular Na+ and Ca2+ overload in astrocytes following oxygen-glucose deprivation (OGD) and reoxygenation (REOX). Here, we further investigated whether NKCC1 and NCX play a role in mitochondrial Ca2+ (Cam2+) overload and dysfunction. OGD/REOX caused a doubling of mitochondrial-releasable Ca2+ (P < 0.05). When NKCC1 was inhibited with bumetanide, the mitochondrial-releasable Ca2+ was reduced by ∼42% (P < 0.05). Genetic ablation of NKCC1 also reduced Cam2+ accumulation. Moreover, OGD/REOX in NKCC1+/+ astrocytes caused dissipation of the mitochondrial membrane potential (Ψm) to 42 ± 3% of controls. In contrast, when NKCC1 was inhibited with bumetanide, depolarization of Ψm was attenuated significantly (66 ± 10% of controls, P < 0.05). Cells were also subjected to severe in vitro hypoxia by superfusion with a hypoxic, acidic, ion-shifted Ringer buffer (HAIR). HAIR/REOX triggered a secondary...
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
44
References
55
Citations
NaN
KQI