| Calmodulin and CaMKII mediate emergent bursting activity in the brainstem respiratory network (preBotC). | |
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MedLine Citation:
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PMID: 23207595 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Emergence of persistent activity in networks can be controlled by intracellular signalling pathways but the mechanisms involved and their role are not yet fully explored. Using calcium imaging and patch-clamp we examined the rhythmic activity in preBötzinger complex (preBötC) in the lower brainstem that generates the respiratory motor output. In the functionally intact acute slices brief hypoxia, electrical stimulation and activation of AMPA receptors transiently depressed bursting activity which then recovered with augmentation. The effects were abrogated after chelation of intracellular calcium and inhibition of L-type calcium channels, calmodulin (CaM) and CaM kinase (CaMKII). Rhythmic calcium transients and synaptic drive currents in preBötC neurons in the organotypic slices showed similar CaM- and CaMKII-dependent responses. The stimuli increased the amplitude of spontaneous and miniature excitatory synaptic currents indicating postsynaptic changes at glutamatergic synapses. In the acute and organotypic slices CaM stimulated and ADP inhibited calcium-dependent TRPM4 channels and CaMKII augmented synaptic drive currents. Experimental data and simulations show the role of ADP and CaMKII in the control of bursting activity and its relation to intracellular signalling. I propose that CaMKII-mediated facilitation of glutamatergic transmission strengthens emergent synchronous activity within preBötC that is then maintained by periodic surges of calcium during the bursts. This may find implications in restoration and consolidation of autonomous activity in the respiratory disorders. |
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Authors:
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Sergej L Mironov |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-12-3 |
Journal Detail:
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Title: The Journal of physiology Volume: - ISSN: 1469-7793 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 2012 Dec |
Date Detail:
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Created Date: 2012-12-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0266262 Medline TA: J Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Georg-August-University. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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