 |
||||
|
||||
|
||||
|
||||
.gif?ad=17923&adview=true)
The Journal of Neuroscience, November 30, 2005, 25(48):11184-11193; doi:10.1523/JNEUROSCI.3370-05.2005
Previous Article | Next Article
Neurobiology of Disease
Calcium- and Metabolic State-Dependent Modulation of the Voltage-Dependent Kv2.1 Channel Regulates Neuronal Excitability in Response to Ischemia
Hiroaki Misonou, Durga P. Mohapatra, Milena Menegola, andJames S. Trimmer Department of Pharmacology, School of Medicine, University of California, Davis, Davis, California 95616
Ischemic stroke is often accompanied by neuronal hyperexcitability (i.e., seizures), which aggravates brain damage. Therefore, suppressing stroke-induced hyperexcitability and associated excitoxicity is a major focus of treatment for ischemic insults. Both ATP-dependent and Ca2+-activated K+ channels have been implicated in protective mechanisms to suppress ischemia-induced hyperexcitability. Here we provide evidence that the localization and function of Kv2.1, the major somatodendritic delayed rectifier voltage-dependent K+ channel in central neurons, is regulated by hypoxia/ischemia-induced changes in metabolic state and intracellular Ca2+ levels. Hypoxia/ischemia in rat brain induced a dramatic dephosphorylation of Kv2.1 and the translocation of surface Kv2.1 from clusters to a uniform localization. In cultured rat hippocampal neurons, chemical ischemia (CI) elicited a similar dephosphorylation and translocation of Kv2.1. These events were reversible and were mediated by Ca2+ release from intracellular stores and calcineurin-mediated Kv2.1 dephosphorylation. CI also induced a hyperpolarizing shift in the voltage-dependent activation of neuronal delayed rectifier currents (IK), leading to enhanced IK and suppressed neuronal excitability. The IK blocker tetraethylammonium reversed the ischemia-induced suppression of excitability and aggravated ischemic neuronal damage. Our results show that Kv2.1 can act as a novel Ca2+- and metabolic state-sensitive K+ channel and suggest that dynamic modulation of IK/Kv2.1 in response to hypoxia/ischemia suppresses neuronal excitability and could confer neuroprotection in response to brief ischemic insults.
Key words: channel; epilepsy; hypoxia; ion channels; hippocampus; neurons; neuroprotection
Received April 7, 2005; revised September 26, 2005; accepted October 15, 2005.
This article has been cited by other articles:
P. J. Mulholland, E. P. Carpenter-Hyland, M. C. Hearing, H. C. Becker, J. J. Woodward, and L. J. Chandler
Glutamate Transporters Regulate Extrasynaptic NMDA Receptor Modulation of Kv2.1 Potassium Channels
J. Neurosci., August 27, 2008; 28(35): 8801 - 8809.
[Abstract] [Full Text] [PDF]
H. Misonou, S. M. Thompson, and X. Cai
Dynamic Regulation of the Kv2.1 Voltage-Gated Potassium Channel during Brain Ischemia through Neuroglial Interaction
J. Neurosci., August 20, 2008; 28(34): 8529 - 8538.
[Abstract] [Full Text] [PDF]
D. P. Mohapatra, D. F. Siino, and J. S. Trimmer
Interdomain Cytoplasmic Interactions Govern the Intracellular Trafficking, Gating, and Modulation of the Kv2.1 Channel
J. Neurosci., May 7, 2008; 28(19): 4982 - 4994.
[Abstract] [Full Text] [PDF]
K.-S. Park, J.-W. Yang, E. Seikel, and J. S. Trimmer
Potassium Channel Phosphorylation in Excitable Cells: Providing Dynamic Functional Variability to a Diverse Family of Ion Channels
Physiology, February 1, 2008; 23(1): 49 - 57.
[Abstract] [Full Text] [PDF]
K. M. S. O'Connell, J. D. Whitesell, and M. M. Tamkun
Localization and mobility of the delayed-rectifer K+ channel Kv2.1 in adult cardiomyocytes
Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H229 - H237.
[Abstract] [Full Text] [PDF]
M. M. Tamkun, K. M. S. O'Connell, and A. S. Rolig
A cytoskeletal-based perimeter fence selectively corrals a sub-population of cell surface Kv2.1 channels
J. Cell Sci., July 15, 2007; 120(14): 2413 - 2423.
[Abstract] [Full Text] [PDF]
L. Neshatian, Y. M. Leung, Y. Kang, X. Gao, H. Xie, R. G. Tsushima, H. Y. Gaisano, and N. E. Diamant
Distinct modulation of Kv1.2 channel gating by wild type, but not open form, of syntaxin-1A
Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1233 - G1242.
[Abstract] [Full Text] [PDF]
H. Misonou, M. Menegola, D. P. Mohapatra, L. K. Guy, K.-S. Park, and J. S. Trimmer
Bidirectional Activity-Dependent Regulation of Neuronal Ion Channel Phosphorylation
J. Neurosci., December 27, 2006; 26(52): 13505 - 13514.
[Abstract] [Full Text] [PDF]
D. J. Schulz, R. A. Baines, C. M. Hempel, L. Li, B. Liss, and H. Misonou
Cellular Excitability and the Regulation of Functional Neuronal Identity: From Gene Expression to Neuromodulation
J. Neurosci., October 11, 2006; 26(41): 10362 - 10367.
[Full Text] [PDF]
Z. Tiran, A. Peretz, T. Sines, V. Shinder, J. Sap, B. Attali, and A. Elson
Tyrosine Phosphatases {varepsilon} and {alpha} Perform Specific and Overlapping Functions in Regulation of Voltage-gated Potassium Channels in Schwann Cells
Mol. Biol. Cell, October 1, 2006; 17(10): 4330 - 4342.
[Abstract] [Full Text] [PDF]
K. M. S. O'Connell, A. S. Rolig, J. D. Whitesell, and M. M. Tamkun
Kv2.1 potassium channels are retained within dynamic cell surface microdomains that are defined by a perimeter fence.
J. Neurosci., September 20, 2006; 26(38): 9609 - 9618.
[Abstract] [Full Text] [PDF]
K.-S. Park, D. P. Mohapatra, H. Misonou, and J. S. Trimmer
Graded regulation of the Kv2.1 potassium channel by variable phosphorylation.
Science, August 18, 2006; 313(5789): 976 - 979.
[Abstract] [Full Text] [PDF]
D. P. Mohapatra and J. S. Trimmer
The Kv2.1 C Terminus Can Autonomously Transfer Kv2.1-Like Phosphorylation-Dependent Localization, Voltage-Dependent Gating, and Muscarinic Modulation to Diverse Kv Channels
J. Neurosci., January 11, 2006; 26(2): 685 - 695.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|