Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiation
Article first published online: 8 AUG 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 107, Issue 3, pages 589–601, November 2008
How to Cite
Olsen, M. L. and Sontheimer, H. (2008), Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiation. Journal of Neurochemistry, 107: 589–601. doi: 10.1111/j.1471-4159.2008.05615.x
- Issue published online: 14 OCT 2008
- Article first published online: 8 AUG 2008
- Received April 30, 2008; revised manuscript received July 18, 2008; accepted August 5, 2008.
- brain tumor;
- cell proliferation;
- ion channel;
- K+ buffering
Astrocytes and oligodendrocytes are characterized by a very negative resting potential and a high resting permeability for K+ ions. Early pharmacological and biophysical studies suggested that the resting potential is established by the activity of inwardly rectifying, Ba2+ sensitive, weakly rectifying Kir channels. Molecular cloning has identified 16 Kir channels genes of which several mRNA transcripts and protein products have been identified in glial cells. However, genetic deletion and siRNA knock-down studies suggest that the resting conductance of astrocytes and oligodendrocytes is largely due to Kir4.1. Loss of Kir4.1 causes membrane depolarization, and a break-down of K+ and glutamate homeostasis which results in seizures and wide-spread white matter pathology. Kir channels have also been shown to act as critical regulators of cell division whereby Kir function is correlated with an exit from the cell cycle. Conversely, loss of functional Kir channels is associated with re-entry of cells into the cell cycle and gliosis. A loss of functional Kir channels has been shown in a number of neurological diseases including temporal lobe epilepsy, amyotrophic lateral sclerosis, retinal degeneration and malignant gliomas. In the latter, expression of Kir4.1 is sufficient to arrest the aberrant growth of these glial derived tumor cells. Kir4.1 therefore represents a potential therapeutic target in a wide variety of neurological conditions.