Recent studies show that glial cells in culture express a variety of voltage-activated ion channels. Oligodendrocytes express predominantly K+ channels, whereas astrocytes, in addition to various forms of K+ channels, also express channels previously thought to be restricted to excitable cells, namely voltage-activated Na+ and Ca+ channels. The P.I. has shown that glial ion channel expression in vitro is dynamic and can be influenced by developmental stage and by environmental factors. For example the presence of neurons alters channel expression of astrocytes in vitro. Evidence for the expression of voltage-activated channels in glial cells is exclusively derived from in vitro studies, and voltage-activated ion channels were not seen in earlier studies on glial cells in vivo leading to controversies as to whether such glial channels might be an artifact of tissue culture. Alternatively, patch-clamp recording in vitro, offering higher resolution than traditional electrode studies used in vivo, may account for the differences observed. The proposed project aims to characterize the electrophysiological properties of glial cells in situ, in hippocampal brain slices, and to compare these findings to the properties of cultured hippocampal glial cells. The P.I. will test the general hypothesis that glial cells in the rat hippocampus in situ do express voltage-activated ion channels, and that their channel complement changes during postnatal development. Using the patch-clamp technique, channel expression will be characterized from identified glial cells in defined regions of the hippocampus (namely stratum moleculare, stratum pyramidale and stratum radiatum of CAl and CA3 respectively) and these studies will be obtained at defined developmental stages (P0-P28). Thus, these studies will assess i.) regional diversity and specialization of channel expression and ii.) possible developmental alterations of channel expression in glial cells. Little is known about functional roles of glial ion channels, however, much has been speculated about roles of glial K+ channels in the regulation of [K+]o. Experiments are proposed to study the contribution of glial K+ channels to [K+]o homeostasis. The role of glial Na+ and Ca2+ channels is entirely unknown. In this proposal, a potential role of glial Na+ channels in basic cell function is hypothesized, namely that Na+ channels constitute a return pathway for Na+ ions in the Na+/K+-ATPase cycle. It is proposed to test this hypothesis using radio-ligand tracer studies and electrophysiological recordings of astrocytes in vitro.
| Thompson, Emily G; Sontheimer, Harald (2016) A role for ion channels in perivascular glioma invasion. Eur Biophys J 45:635-648 |
| Kimbrough, Ian F; Robel, Stefanie; Roberson, Erik D et al. (2015) Vascular amyloidosis impairs the gliovascular unit in a mouse model of Alzheimer's disease. Brain 138:3716-33 |
| Robert, Stephanie M; Buckingham, Susan C; Campbell, Susan L et al. (2015) SLC7A11 expression is associated with seizures and predicts poor survival in patients with malignant glioma. Sci Transl Med 7:289ra86 |
| Robel, Stefanie; Buckingham, Susan C; Boni, Jessica L et al. (2015) Reactive astrogliosis causes the development of spontaneous seizures. J Neurosci 35:3330-45 |
| Robert, Stephanie M; Ogunrinu-Babarinde, Toyin; Holt, Kenneth T et al. (2014) Role of glutamate transporters in redox homeostasis of the brain. Neurochem Int 73:181-91 |
| Turner, Kathryn L; Sontheimer, Harald (2014) KCa3.1 modulates neuroblast migration along the rostral migratory stream (RMS) in vivo. Cereb Cortex 24:2388-400 |
| Watkins, Stacey; Robel, Stefanie; Kimbrough, Ian F et al. (2014) Disruption of astrocyte-vascular coupling and the blood-brain barrier by invading glioma cells. Nat Commun 5:4196 |
| Honasoge, Avinash; Shelton, Katherine A; Sontheimer, Harald (2014) Autocrine regulation of glioma cell proliferation via pHe-sensitive K(+) channels. Am J Physiol Cell Physiol 306:C493-505 |
| Robert, Stephanie M; Sontheimer, Harald (2014) Glutamate transporters in the biology of malignant gliomas. Cell Mol Life Sci 71:1839-54 |
| Cuddapah, Vishnu Anand; Robel, Stefanie; Watkins, Stacey et al. (2014) A neurocentric perspective on glioma invasion. Nat Rev Neurosci 15:455-65 |
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