cAMP/protein kinase A signalling pathway protects against neuronal apoptosis and is associated with modulation ofKv2.1in cerebellar granule cells
| العنوان: | cAMP/protein kinase A signalling pathway protects against neuronal apoptosis and is associated with modulation ofKv2.1in cerebellar granule cells |
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| المؤلفون: | Zhi-Hong Zhang, Yu Ding, Yu-Qiu Zhang, Wen-Hua Ren, Yan-Ai Mei, Song Jiao, Zheng Liu |
| المصدر: | Journal of Neurochemistry. 100:979-991 |
| بيانات النشر: | Wiley, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | medicine.medical_specialty, Small interfering RNA, Patch-Clamp Techniques, Protein subunit, Apoptosis, Biology, Transfection, Biochemistry, Membrane Potentials, Potassium Chloride, Cellular and Molecular Neuroscience, chemistry.chemical_compound, Shab Potassium Channels, Cerebellum, Internal medicine, Cyclic AMP, medicine, Animals, Gene silencing, Drug Interactions, Enzyme Inhibitors, RNA, Small Interfering, Protein kinase A, Cells, Cultured, Neurons, Forskolin, Dose-Response Relationship, Drug, Reverse Transcriptase Polymerase Chain Reaction, Colforsin, Dose-Response Relationship, Radiation, Cyclic AMP-Dependent Protein Kinases, Electric Stimulation, Hedgehog signaling pathway, Rats, Cell biology, medicine.anatomical_structure, Endocrinology, Animals, Newborn, chemistry, Neuron |
| الوصف: | Previously, we have reported that apoptosis of cerebellar granular neurons induced by incubation in 5 mm K(+) and serum-free medium (LK-S) was associated with an increase in the delayed rectifier K(+) current (I(K)). Here, we show that I(K) associated with apoptotic neurons is mainly encoded by a Kv2.1 subunit. Silencing Kv2.1 expression by small interfering RNA reduces I(K) and increases neuron viability. Forskolin is able to decrease the I(K) amplitude recording from neurons of both the LK-S and control group, and prevents apoptosis of granule cells that are induced by LK-S. Dibutyryl cAMP mimicks the effect of forskolin on the modulation of I(K) and, accordingly, the inhibitor of protein kinase A, H-89, aborts the neuron-protective effect induced by forskolin. Whereas the expression of Kv2.1 was silenced by Kv2.1 small interfering RNA, the inhibition of forskolin on the current amplitude was significantly reduced. Quantitative RT-PCR and whole-cell recording revealed that the expression of Kv2.1 was elevated in the apoptotic neurons, and forskolin significantly depressed the expression of Kv2.1. We conclude that the protection against apoptosis via the protein kinase A pathway is associated with a double modulation on I(K) channel properties and its expression of alpha-subunit that is mainly encoded by the Kv2.1 gene. |
| تدمد: | 1471-4159 0022-3042 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3ca82f0a5e6c892c16be55eb1d53a1baTest https://doi.org/10.1111/j.1471-4159.2006.04261.xTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3ca82f0a5e6c892c16be55eb1d53a1ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14714159 00223042 |
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