WWW.JNEUROSCI.ORG
-
The Journal of Neuroscience
QUICK SEARCH:   [advanced]


     
-


HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP
The Journal of Neuroscience, June 13, 2007, 27(24):6388-6399; doi:10.1523/JNEUROSCI.1190-07.2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Submit an eLetter
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Clancy, S. M.
Right arrow Articles by Slesinger, P. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Clancy, S. M.
Right arrow Articles by Slesinger, P. A.

 Previous Article  |  Next Article 

Cellular/Molecular
Coregulation of Natively Expressed Pertussis Toxin-Sensitive Muscarinic Receptors with G-Protein-Activated Potassium Channels

Sinead M. Clancy,1  Stephanie B. Boyer,1,2 and Paul A. Slesinger1,2

1Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, and 2Department of Neurosciences, University of California, San Diego, La Jolla, California 92093

Correspondence should be addressed to Paul A. Slesinger, Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037. Email: slesinger{at}salk.edu

Many inhibitory neurotransmitters in the brain activate Kir3 channels by stimulating pertussis toxin (PTX)-sensitive G-protein-coupled receptors. Here, we investigated the regulation of native muscarinic receptors and Kir3 channels expressed in NGF-differentiated PC12 cells, which are similar to sympathetic neurons. Quantitative reverse transcription-PCR and immunocytochemistry revealed that NGF treatment significantly upregulated mRNA and protein for m2 muscarinic receptors, PTX-sensitive G{alpha}o G-proteins, and Kir3.2c channels. Surprisingly, these upregulated muscarinic receptor/Kir3 signaling complexes were functionally silent. Ectopic expression of m2 muscarinic receptors or Kir3.2c channels was unable to produce muscarinic receptor-activated Kir3 currents with oxotremorine. Remarkably, pretreatment with muscarinic (m2/m4) receptor antagonists resulted in robust oxotremorine-activated Kir3 currents. Thus, sustained cholinergic stimulation of natively expressed m2/m4 muscarinic receptors controlled cell surface expression and functional coupling of both receptors and Kir3 channels. This new pathway for controlling Kir3 signaling could help limit the potential harmful effects of excessive Kir3 activity in the brain.

Key words: Kir3; NGF; heterologous regulation; muscarinic GPCR; complex; pertussis toxin

Received Nov. 27, 2006; revised April 27, 2007; accepted May 2, 2007.

Correspondence should be addressed to Paul A. Slesinger, Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037. Email: slesinger{at}salk.edu






 -
-

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help
-
Copyright 2009 by Society for Neuroscience ONLINE ISSN: 1529-2401
-