Multifaceted Modulation of K+ Channels by Protein-tyrosine Phosphatase ϵ Tunes Neuronal Excitability
| Autor: | Polina Kornilov, Sharon Ebner-Bennatan, Zohar Tiran, Eti Patrich, Ari Elson, Asher Peretz, Bernard Attali |
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| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
animal structures Nerve Tissue Proteins CHO Cells Protein tyrosine phosphatase Biology environment and public health Biochemistry Membrane Potentials Dephosphorylation Mice chemistry.chemical_compound Cricetulus Neurobiology Cricetinae Internal medicine medicine Animals Phosphorylation Molecular Biology Cerebral Cortex Mice Knockout Neurons Membrane potential Kinase Receptor-Like Protein Tyrosine Phosphatases Class 4 Tyrosine phosphorylation Cell Biology Potassium channel Cell biology enzymes and coenzymes (carbohydrates) Endocrinology nervous system chemistry Potassium Channels Voltage-Gated Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Biological Chemistry. 287:27614-27628 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m112.342519 |
| Popis: | Non-receptor-tyrosine kinases (protein-tyrosine kinases) and non-receptor tyrosine phosphatases (PTPs) have been implicated in the regulation of ion channels, neuronal excitability, and synaptic plasticity. We previously showed that protein-tyrosine kinases such as Src kinase and PTPs such as PTPα and PTPε modulate the activity of delayed-rectifier K(+) channels (I(K)). Here we show cultured cortical neurons from PTPε knock-out (EKO) mice to exhibit increased excitability when compared with wild type (WT) mice, with larger spike discharge frequency, enhanced fast after-hyperpolarization, increased after-depolarization, and reduced spike width. A decrease in I(K) and a rise in large-conductance Ca(2+)-activated K(+) currents (mBK) were observed in EKO cortical neurons compared with WT. Parallel studies in transfected CHO cells indicate that Kv1.1, Kv1.2, Kv7.2/7.3, and mBK are plausible molecular correlates of this multifaceted modulation of K(+) channels by PTPε. In CHO cells, Kv1.1, Kv1.2, and Kv7.2/7.3 K(+) currents were up-regulated by PTPε, whereas mBK channel activity was reduced. The levels of tyrosine phosphorylation of Kv1.1, Kv1.2, Kv7.3, and mBK potassium channels were increased in the brain cortices of neonatal and adult EKO mice compared with WT, suggesting that PTPε in the brain modulates these channel proteins. Our data indicate that in EKO mice, the lack of PTPε-mediated dephosphorylation of Kv1.1, Kv1.2, and Kv7.3 leads to decreased I(K) density and enhanced after-depolarization. In addition, the deficient PTPε-mediated dephosphorylation of mBK channels likely contributes to enhanced mBK and fast after-hyperpolarization, spike shortening, and consequent increase in neuronal excitability observed in cortical neurons from EKO mice. |
| Databáze: | OpenAIRE |
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