| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Neurosurgery, Univ. of Wisconsin Medical School, Madison, WI, USA
2 Molecular Genetics, Biochemistry and Microbiology, Univ. of Cincinnati, Cincinnati, WI, USA
3 Neurosurgery, Univ. of Wisconsin Medical School, Madison, WI, USA; Physiology, Univ. of Wisconsin Medical School, Madison, WI, USA
* To whom correspondence should be addressed. E-mail: sun{at}neurosurg.wisc.edu.
We reported that Na/H exchanger isoform 1 (NHE1) activity in astrocytes is stimulated and leads to intracellular Na+ loading following oxygen and glucose deprivation (OGD) (Kintner et al., 2004). However, the underlying mechanisms for this stimulation of NHE1 activity and its impact on astrocyte function are unknown. In the present study, we investigated the role for extracellular signal-regulatory protein kinase (ERK1/2) pathway in NHE1 activation. NHE1 activity was elevated by ~ 75% in NHE1+/+ astrocytes following 2 h OGD and 1 h reoxygenation (OGD/REOX). The OGD/REOX-mediated stimulation of NHE1 was partially blocked by 30 µM PD98059. Increased expression of phosphorylated ERK 1/2 was detected in NHE1+/+ astrocytes following OGD/REOX. Moreover, stimulation of NHE1 activity not only disrupted Na+ but also Ca2+ homeostasis via reverse-mode operation of Na+/Ca2+ exchange. OGD/REOX led to 103% increase in [Ca2+]i in NHE1+/+ astrocytes in the presence of thaspsigargin. Inhibition of NHE1 activity with NHE1 inhibitor HOE 642 decreased OGD/REOX-induced elevation of [Ca2+]i by 73%. To further investigate changes of Ca2+ signaling, bradykinin-mediated Ca2+ release was evaluated. Bradykinin-mediated Ca2+i transient in NHE1+/+ astrocytes was increased by ~84% following OGD/REOX. However, in NHE1-/- astrocytes or NHE1+/+ astrocytes treated with HOE 642, the bradykinin-induced Ca2+ release was only increased by ~ 34%. Inhibition of the reverse mode of Na+/Ca2+ exchange abolished OGD/REOX-mediated Ca2+ rise. Taken together, our data suggest that ERK1/2 is involved in activation of NHE1 in astrocytes following in vitro ischemia. NHE1-mediated Na+ accumulation subsequently alters Ca2+ homeostasis via Na+/Ca2+ exchange.
This article has been cited by other articles:
|
|
 |
|
  S. Hom, M. A. Fleegal, R. D. Egleton, C. R. Campos, B. T. Hawkins, and T. P. Davis Comparative changes in the blood-brain barrier and cerebral infarction of SHR and WKY rats Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2007; 292(5): R1881 - R1892. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. B. Kintner, J. Luo, J. Gerdts, A. J. Ballard, G. E. Shull, and D. Sun Role of Na+-K+-Cl- cotransport and Na+/Ca2+ exchange in mitochondrial dysfunction in astrocytes following in vitro ischemia Am J Physiol Cell Physiol, March 1, 2007; 292(3): C1113 - C1122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. F. Pedersen, M. E. O'Donnell, S. E. Anderson, and P. M. Cala Physiology and pathophysiology of Na+/H+ exchange and Na+-K+-2Cl- cotransport in the heart, brain, and blood Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2006; 291(1): R1 - R25. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Luo, H. Chen, D. B. Kintner, G. E. Shull, and D. Sun Decreased Neuronal Death in Na+/H+ Exchanger Isoform 1-Null Mice after In Vitro and In Vivo Ischemia J. Neurosci., December 7, 2005; 25(49): 11256 - 11268. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
