Stimulation of bursting in pre-Bötzinger neurons by Epac through calcium release and modulation of TRPM4 and K-ATP channels
| Autor: | Sergej L, Mironov, Ekaterina Y, Skorova |
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| Rok vydání: | 2011 |
| Předmět: |
6-Cyano-7-nitroquinoxaline-2
3-dione Neurons Phosphatidylinositol 4 5-Diphosphate Patch-Clamp Techniques Dose-Response Relationship Drug TRPM Cation Channels In Vitro Techniques Bradykinin Biophysical Phenomena Pyrrolidinones Membrane Potentials Androstadienes Mice Animals Newborn KATP Channels Cyclic AMP Fluorescence Resonance Energy Transfer Animals Calcium Drug Interactions Enzyme Inhibitors Estrenes Wortmannin Excitatory Amino Acid Antagonists Brain Stem |
| Zdroj: | Journal of neurochemistry. 117(2) |
| ISSN: | 1471-4159 |
| Popis: | The exchange factor directly activated by cAMP (Epac) can couple cAMP production to the activation of particular membrane and cytoplasmic targets. Using patch-clamp recordings and calcium imaging in organotypic brainstem slices, we examined the role of Epac in pre-Bötzinger complex, an essential part of the respiratory network. The selective agonist 8-(4-chlorophenylthio)-2'-O-methyl-cAMP (8-pCPT) sensitized calcium mobilisation from inositol-1,4,5-trisphosphate-sensitive internal stores that stimulated TRPM4 (transient receptor potential cation channel, subfamily M, Melastatin) channels and potentiated the bursts of action potentials. 8-pCPT actions were abolished after inhibition of phospholipase C with U73122 and depletion of calcium stores with thapsigargin. Caffeine-sensitive release channels were not modulated by 8-pCPT. Epac inhibited ATP-sensitive K(+) channels that also led to the enhancement of bursting by 8-pCPT. Bursting activity, spontaneous calcium transients and activity of TRPM4 and ATP-sensitive K(+) channels were potentiated after brief exposures to bradykinin and incubation with wortmannin produced opposite effects that can be explained by changes in phosphatidylinositol 4,5-bisphosphate levels. 8-pCPT stimulated the respiratory motor output in functionally intact preparations and the effects of bradykinin and wortmannin were identical to those observed in organotypic slices. The data thus indicate a novel pathway of controlling bursting activity in pre-Bötzinger complex neurons through Epac that can involved in reinforcement of the respiratory activity by cAMP. |
| Databáze: | OpenAIRE |
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