Altered phosphorylation and localization of the A-type channel, Kv4.2 in status epilepticus
Article first published online: 30 MAY 2008
© 2008 The Authors. Journal Compilation © 2008 International Society for Neurochemistry
Journal of Neurochemistry
Volume 106, Issue 4, pages 1929–1940, August 2008
How to Cite
Lugo, J. N., Barnwell, L. F., Ren, Y., Lee, W. L., Johnston, L. D., Kim, R., Hrachovy, R. A., Sweatt, J. D. and Anderson, A. E. (2008), Altered phosphorylation and localization of the A-type channel, Kv4.2 in status epilepticus. Journal of Neurochemistry, 106: 1929–1940. doi: 10.1111/j.1471-4159.2008.05508.x
- Issue published online: 1 AUG 2008
- Article first published online: 30 MAY 2008
- Received April 11, 2008; revised manuscript received May 23, 2008; accepted May 23, 2008.
- extracellular signal-regulated kinase;
- ion channels;
- mitogen-activated protein kinase;
- protein phosphorylation;
Extracelluar signal-regulated kinase (ERK) pathway activation has been demonstrated following convulsant stimulation; however, little is known about the molecular targets of ERK in seizure models. Recently, it has been shown that ERK phosphorylates Kv4.2 channels leading to down-regulation of channel function, and substantially alters dendritic excitability. In the kainate model of status epilepticus (SE), we investigated whether ERK phosphorylates Kv4.2 and whether the changes in Kv4.2 were evident at a synaptosomal level during SE. Western blotting was performed on rat hippocampal whole cell, membrane, synaptosomal, and surface biotinylated extracts following systemic kainate using an antibody generated against the Kv4.2 ERK sites and for Kv4.2, ERK, and phospho-ERK. ERK activation was associated with an increase in Kv4.2 phosphorylation during behavioral SE. During SE, ERK activation and Kv4.2 phosphorylation were evident at the whole cell and synaptosomal levels. In addition, while whole-cell preparations revealed no alterations in total Kv4.2 levels, a decrease in synaptosomal and surface expression of Kv4.2 was evident after prolonged SE. These results demonstrate ERK pathway coupling to Kv4.2 phosphorylation. The finding of decreased Kv4.2 levels in hippocampal synaptosomes and surface membranes suggest additional mechanisms for decreasing the dendritic A-current, which could lead to altered intrinsic membrane excitability during SE.