Tags

Type your tag names separated by a space and hit enter

Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia.
Am J Physiol Cell Physiol. 2007 Mar; 292(3):C1113-22.AJ

Abstract

Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) and reverse mode operation of the Na(+)/Ca(2+) exchanger (NCX) contribute to intracellular Na(+) and Ca(2+) overload in astrocytes following oxygen-glucose deprivation (OGD) and reoxygenation (REOX). Here, we further investigated whether NKCC1 and NCX play a role in mitochondrial Ca(2+) (Ca(m)(2+)) overload and dysfunction. OGD/REOX caused a doubling of mitochondrial-releasable Ca(2+) (P < 0.05). When NKCC1 was inhibited with bumetanide, the mitochondrial-releasable Ca(2+) was reduced by approximately 42% (P < 0.05). Genetic ablation of NKCC1 also reduced Ca(m)(2+) accumulation. Moreover, OGD/REOX in NKCC1(+/+) astrocytes caused dissipation of the mitochondrial membrane potential (Psi(m)) to 42 +/- 3% of controls. In contrast, when NKCC1 was inhibited with bumetanide, depolarization of Psi(m) 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, sustained rise in intracellular Ca(2+) that was attenuated by reversal NCX inhibitor KB-R7943. The hypoxia-mediated increase in Ca(m)(2+) was accompanied by loss of Psi(m) and cytochrome c release in NKCC1(+/+) astrocytes. Bumetanide or genetic ablation of NKCC1 attenuated mitochondrial dysfunction and astrocyte death following ischemia. Our study suggests that NKCC1 acting in concert with NCX causes a perturbation of Ca(m)(2+) homeostasis and mitochondrial dysfunction and cell death following in vitro ischemia.

Authors+Show Affiliations

Dept. of Neurological Surgery, University of Wisconsin School of Medicine, Madison, WI 53792, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17035299

Citation

Kintner, Douglas B., et al. "Role of Na+-K+-Cl- Cotransport and Na+/Ca2+ Exchange in Mitochondrial Dysfunction in Astrocytes Following in Vitro Ischemia." American Journal of Physiology. Cell Physiology, vol. 292, no. 3, 2007, pp. C1113-22.
Kintner DB, Luo J, Gerdts J, et al. Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia. Am J Physiol Cell Physiol. 2007;292(3):C1113-22.
Kintner, D. B., Luo, J., Gerdts, J., Ballard, A. J., Shull, G. E., & Sun, D. (2007). Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia. American Journal of Physiology. Cell Physiology, 292(3), C1113-22.
Kintner DB, et al. Role of Na+-K+-Cl- Cotransport and Na+/Ca2+ Exchange in Mitochondrial Dysfunction in Astrocytes Following in Vitro Ischemia. Am J Physiol Cell Physiol. 2007;292(3):C1113-22. PubMed PMID: 17035299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia. AU - Kintner,Douglas B, AU - Luo,Jing, AU - Gerdts,Josiah, AU - Ballard,Andy J, AU - Shull,Gary E, AU - Sun,Dandan, Y1 - 2006/10/11/ PY - 2006/10/13/pubmed PY - 2007/4/25/medline PY - 2006/10/13/entrez SP - C1113 EP - 22 JF - American journal of physiology. Cell physiology JO - Am J Physiol Cell Physiol VL - 292 IS - 3 N2 - Na(+)-K(+)-Cl(-) cotransporter isoform 1 (NKCC1) and reverse mode operation of the Na(+)/Ca(2+) exchanger (NCX) contribute to intracellular Na(+) and Ca(2+) overload in astrocytes following oxygen-glucose deprivation (OGD) and reoxygenation (REOX). Here, we further investigated whether NKCC1 and NCX play a role in mitochondrial Ca(2+) (Ca(m)(2+)) overload and dysfunction. OGD/REOX caused a doubling of mitochondrial-releasable Ca(2+) (P < 0.05). When NKCC1 was inhibited with bumetanide, the mitochondrial-releasable Ca(2+) was reduced by approximately 42% (P < 0.05). Genetic ablation of NKCC1 also reduced Ca(m)(2+) accumulation. Moreover, OGD/REOX in NKCC1(+/+) astrocytes caused dissipation of the mitochondrial membrane potential (Psi(m)) to 42 +/- 3% of controls. In contrast, when NKCC1 was inhibited with bumetanide, depolarization of Psi(m) 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, sustained rise in intracellular Ca(2+) that was attenuated by reversal NCX inhibitor KB-R7943. The hypoxia-mediated increase in Ca(m)(2+) was accompanied by loss of Psi(m) and cytochrome c release in NKCC1(+/+) astrocytes. Bumetanide or genetic ablation of NKCC1 attenuated mitochondrial dysfunction and astrocyte death following ischemia. Our study suggests that NKCC1 acting in concert with NCX causes a perturbation of Ca(m)(2+) homeostasis and mitochondrial dysfunction and cell death following in vitro ischemia. SN - 0363-6143 UR - https://www.unboundmedicine.com/medline/citation/17035299/Role_of_Na+_K+_Cl__cotransport_and_Na+/Ca2+_exchange_in_mitochondrial_dysfunction_in_astrocytes_following_in_vitro_ischemia_ L2 - https://journals.physiology.org/doi/10.1152/ajpcell.00412.2006?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -