CaMKII is essential for the function of the enteric nervous system

Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are major downstream mediators of neuronal calcium signaling that regulate multiple neuronal functions. CaMKII, one of the key CaMKs, plays a significant role in mediating cellular responses to external signaling molecules. Although calcium signali...

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Bibliographic Details
Published in:PloS one 2012-08, Vol.7 (8), p.e44426-e44426
Main Authors: Gao, Na, Luo, Jialie, Uray, Karen, Qian, Aihua, Yin, Shijin, Wang, Guodu, Wang, Xiyu, Xia, Yun, Wood, Jackie D, Hu, Hongzhen
Format: Article
Language:English
Subjects:
Animals
Biology
Ca2+/calmodulin-dependent protein kinase II
Calcium
Calcium signalling
Calcium-binding protein
Calcium-Calmodulin-Dependent Protein Kinase Type 2 - metabolism
Calmodulin
Calmodulin - metabolism
Calretinin
Colon
Contractility
Enteric nervous system
Enteric Nervous System - cytology
Enteric Nervous System - enzymology
Excitability
Excitatory postsynaptic potentials
Excitatory Postsynaptic Potentials - physiology
Gastrointestinal Motility - physiology
Guinea Pigs
Humans
Immunofluorescence
Immunoreactivity
In Vitro Techniques
Intestinal motility
Intestine
Kinases
Mammals
Metabotropic receptors
Mice
Mice, Inbred C57BL
Motor Neurons - cytology
Motor Neurons - enzymology
Myenteric plexus
Myenteric Plexus - cytology
Myenteric Plexus - enzymology
Nervous system
Neurons
Nitric oxide
Nitric-oxide synthase
Rats
Rats, Sprague-Dawley
Receptors, Purinergic - metabolism
Rodents
Signal Transduction
Small intestine
Species Specificity
Submucosal plexus
Tetrodotoxin
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Summary:Ca(2+)/calmodulin-dependent protein kinases (CaMKs) are major downstream mediators of neuronal calcium signaling that regulate multiple neuronal functions. CaMKII, one of the key CaMKs, plays a significant role in mediating cellular responses to external signaling molecules. Although calcium signaling plays an essential role in the enteric nervous system (ENS), the role of CaMKII in neurogenic intestinal function has not been determined. In this study, we investigated the function and expression pattern of CaMKII in the ENS across several mammalian species. CaMKII expression was characterized by immunofluorescence analyses and Western Blot. CaMKII function was examined by intracellular recordings and by assays of colonic contractile activity. Immunoreactivity for CaMKII was detected in the ENS of guinea pig, mouse, rat and human preparations. In guinea pig ENS, CaMKII immunoreactivity was enriched in both nitric oxide synthase (NOS)- and calretinin-containing myenteric plexus neurons and non-cholinergic secretomotor/vasodilator neurons in the submucosal plexus. CaMKII immunoreactivity was also expressed in both cholinergic and non-cholinergic neurons in the ENS of mouse, rat and human. The selective CaMKII inhibitor, KN-62, suppressed stimulus-evoked purinergic slow EPSPs and ATP-induced slow EPSP-like response in guinea pig submucosal plexus, suggesting that CaMKII activity is required for some metabotropic synaptic transmissions in the ENS. More importantly, KN-62 significantly suppressed tetrodotoxin-induced contractile response in mouse colon, which suggests that CaMKII activity is a major determinant of the tonic neurogenic inhibition of this tissue. ENS neurons across multiple mammalian species express CaMKII. CaMKII signaling constitutes an important molecular mechanism for controlling intestinal motility and secretion by regulating the excitability of musculomotor and secretomotor neurons. These findings revealed a fundamental role of CaMKII in the ENS and provide clues for the treatment of intestinal dysfunctions.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0044426