Tissue-specific regulation of G-protein-coupled inwardly rectifying K+ channel expression by muscarinic receptor activation in ovo.
We investigated the effects of muscarinic acetylcholine receptor stimulation on the expression levels of the G-protein-coupled inwardly rectifying K+ channel (GIRK) subunits using solution hybridization and immunoblot analyses. We report here that treatment of chick embryos in ovo with muscarinic agonist causes decreases in mRNA levels encoding GIRK1 and GIRK4 in atria but does not alter GIRK1 expression in ventricles. In addition, GIRK1 protein levels also demonstrate a decrease in atria upon muscarinic acetylcholine receptor stimulation. Numerous receptors couple to the activation of the GIRK family of inwardly rectifying K+ channels; thus, these decreases represent a novel mechanism for regulating physiological responses to chronic agonist exposure.
Thomas
S L
SL
Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195-7750, USA.
Chmelar
R S
RS
Lu
C
C
Halvorsen
S W
SW
Nathanson
N M
NM
D000818:Animals; D002217:Carbachol / Q000008:administration & dosage / Q000494:pharmacology; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006321:Heart / Q000196:embryology*; D018721:Muscarinic Agonists / Q000008:administration & dosage / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D018721:Muscarinic Agonists; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D002217:Carbachol; D019204:GTP-Binding Proteins