Document Detail


Ether-a-go-go-related gene 3 is the main candidate for the E-4031-sensitive potassium current in the pacemaker interstitial cells of Cajal.
MedLine Citation:
PMID:  18669623     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The interstitial cells of Cajal (ICC), as pacemaker cells of the gut, contribute to rhythmic peristalsis and muscle excitability through initiation of slow-wave activity, which subsequently actively propagates into the musculature. An E-4031-sensitive K(+) current makes a critical contribution to membrane potential in ICC. This study provides novel features of this current in ICC in physiological solutions and seeks to identify the channel isoform. In situ hybridization and Kit immunohistochemistry were combined to assess ether-a-go-go-related gene (ERG) mRNA expression in ICC in mouse jejunum, while the translated message was assessed by immunofluorescence colocalization of ERG and Kit proteins. E-4031-sensitive currents in cultured ICC were studied by the whole cell patch-clamp method, with physiological K(+) concentration in the bath and the pipette. In situ hybridization combined with Kit immunohistochemistry detected m-erg1 and m-erg3, but not m-erg2, mRNA in ICC. ERG3 protein was colocalized with Kit-immunoreactive ICC in jejunum sections, but ERG1 protein was visualized only in the smooth muscle cells. At physiological K(+) concentration, the E-4031-sensitive outward current in ICC was different from its counterpart in cardiac and gut smooth muscle cells. In particular, inactivation upon depolarization and recovery from inactivation by hyperpolarization were modest in ICC. In summary, the E-4031-sensitive currents influence the kinetics of the pacemaker activity in ICC and contribute to maintenance of the resting membrane potential in smooth muscle cells, which together constitute a marked effect on tissue excitability. Whereas this current is mediated by ERG1 in smooth muscle, it is primarily mediated by ERG3 in ICC.
Authors:
Elizabeth J White; Sung Jin Park; Jane A Foster; Jan D Huizinga
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-31
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  295     ISSN:  0193-1857     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2008 Oct 
Date Detail:
Created Date:  2008-10-16     Completed Date:  2008-11-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G691-9     Citation Subset:  IM    
Affiliation:
Dept. of Medicine, McMaster Univ., 1200 Main St. West, HSC-3N8, Hamilton, ON, Canada L8N 3Z5.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cells, Cultured
Gastrointestinal Motility / physiology*
Jejunum / cytology,  physiology*
Mice
Patch-Clamp Techniques
Piperidines / pharmacology*
Potassium Channels / drug effects,  physiology*
Pyridines / pharmacology*
Chemical
Reg. No./Substance:
0/Erg3 protein, mouse; 0/Piperidines; 0/Potassium Channels; 0/Pyridines; 113558-89-7/E 4031

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