Stimulation of bursting in pre-Bötzinger neurons by Epac through calcium release and modulation of TRPM4 and K-ATP channels
Version of Record online: 24 FEB 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 117, Issue 2, pages 295–308, April 2011
How to Cite
Mironov, S. L. and Skorova, E. Y. (2011), Stimulation of bursting in pre-Bötzinger neurons by Epac through calcium release and modulation of TRPM4 and K-ATP channels. Journal of Neurochemistry, 117: 295–308. doi: 10.1111/j.1471-4159.2011.07202.x
- Issue online: 1 APR 2011
- Version of Record online: 24 FEB 2011
- Accepted manuscript online: 31 JAN 2011 11:41PM EST
- Received September 21, 2010; revised manuscript received/accepted January 24, 2011.
- bursting activity;
- internal calcium stores;
- K-ATP channels;
- respiratory network;
- TRPM4 channels
J. Neurochem. (2011) 117, 295–308.
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.