Studies are proposed on Na, K-ATPase in optic nerve head astrocytes. The ability of astrocytes to regulate pH, potassium, calcium and glutamate in the neuronal microenvironment is linked to Na, K-ATPase. Astrocytes express two Na,K-ATPase isoforms alpha1 and alpha2. The two isoforms appears to have different functions but we do not have complete information on their respective roles or the implications for astrocyte physiology. Na,K-ATPase alpha1 has a vital housekeeping function, regulating the cell-wide concentration of cytoplasmic sodium. We are particularly interested in the Na,K-ATPase alpha2 isoform because Preliminary Studies suggest it has a different role. It does not appear control cell-wide sodium concentration but instead we think Na,K-ATPase alpha2 may be specialized in a way that causes it to have a major influence on glutamate uptake, cell calcium balance and possibly cell growth. Experiments are proposed to study how and astrocytes has the potential to impair the ability of the cell to accumulate extracellular potassium, transport glutamate and protons and regulate cytoplasmic calcium. We also propose studies to examine the potential impairment of Na,K-ATPase function by in vitro episodes of ATP depletion and nitric oxide exposure and by elevated intracellular pressure in vivo.
The aims are:
(AIM 1) Determine the influence of Na, K-ATPase alpha2 activity on glutamate uptake;
(AIM 2) Determine how altered Na,K-ATPase alpha2 activity leads to changes in cytoplasmic calcium stores and subsequent changes in astrocyte behavior;
(AIM 3) Study how abnormal Na,K-ATPase activity could impact proton transport mechanisms;
(AIM 4) Study the factors that cause abnormal Na,K-ATPase function or expression.
| Mandal, Amritlal; Shahidullah, Mohammad; Delamere, Nicholas A (2010) Hydrostatic pressure-induced release of stored calcium in cultured rat optic nerve head astrocytes. Invest Ophthalmol Vis Sci 51:3129-38 |
| Mandal, Amritlal; Shahidullah, Mohammad; Delamere, Nicholas A et al. (2009) Elevated hydrostatic pressure activates sodium/hydrogen exchanger-1 in rat optic nerve head astrocytes. Am J Physiol Cell Physiol 297:C111-20 |
| Mandal, Amritlal; Delamere, Nicholas A; Shahidullah, Mohammad (2008) Ouabain-induced stimulation of sodium-hydrogen exchange in rat optic nerve astrocytes. Am J Physiol Cell Physiol 295:C100-10 |
| Khundmiri, Syed J; Amin, Vishal; Henson, Jeff et al. (2007) Ouabain stimulates protein kinase B (Akt) phosphorylation in opossum kidney proximal tubule cells through an ERK-dependent pathway. Am J Physiol Cell Physiol 293:C1171-80 |
