Modulation of H-channels in Hippocampal Pyramidal Neurons by P38 Mitogen-activated Protein Kinase.
From: Department of Neurology and Regional Epilepsy Center, Neurobiology and Behavior Program, University of Washington, Seattle, Washington 98104, USA. npoolos@u.washington.edu
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Jul 2006
- ISSN: 1529-2401
- Volume: 26
- Issue: 30
- Pages: 7995-8003
- Medium: Internet
- Language: English
- Citation (JAMA): Poolos Nicholas P, Bullis James B, Roth Miranda K, et al. Modulation of H-channels in Hippocampal Pyramidal Neurons by P38 Mitogen-activated Protein Kinase.. J. Neurosci. Jul 2006;26:7995-8003
Abstract
Hyperpolarization-activated cyclic nucleotide-gated ion channels (h-channels; I(h); HCN) modulate intrinsic excitability in hippocampal and neocortical pyramidal neurons, among others. Whereas I(h) mediated by the HCN2 isoform is regulated by cAMP, there is little known about kinase modulation of I(h), especially for the HCN1 isoform predominant in pyramidal neurons. We used a computational method to identify a novel kinase modulator of h-channels, p38 mitogen-activated protein kinase (p38 MAPK). Inhibition of p38 MAPK in hippocampal pyramidal neurons caused a approximately 25 mV hyperpolarization of I(h) voltage-dependent activation. This downregulation of I(h) produced hyperpolarization of resting potential, along with increased input resistance and temporal summation of excitatory inputs. Activation of p38 MAPK caused a approximately 11 mV depolarizing shift in I(h) activation, along with depolarized resting potential, and decreased input resistance and temporal summation. Inhibition of related MAPKs, ERK1/2 (extracellular signal-related kinase 1/2) and JNK (c-Jun N-terminal kinase), produced no effect on I(h). These results show that p38 MAPK is a strong modulator of h-channel biophysical properties and may deserve additional exploration as a link between altered I(h) and pathological conditions such as epilepsy.
Mesh Headings (Keywords): Adaptation, Physiological, Animals, Cells, Cultured, Cyclic Nucleotide-Gated Cation Channels, Hippocampus, Ion Channel Gating, Ion Channels, Male, Potassium Channels, Pyramidal Cells, Rats, Rats, Sprague-Dawley, p38 Mitogen-Activated Protein Kinases
Check for Full Text / PubMed Unique Identifier (PMID): 16870744
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