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Abstract
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.
Highlights
Muscarinic acetylcholine receptors1 couple to heterotrimeric G-proteins to regulate multiple effector molecules such as the G-protein-coupled inwardly rectifying K؉ channel (GIRK) family of inwardly rectifying Kϩ channels and the enzymes adenylyl cyclase and phospholipase C
GIRK mRNA Expression in Chick Atria and Ventricles—We determined the amounts of GIRK1 and GIRK4 mRNA expression in embryonic day 9 chick atria and ventricles using solution hybridization
No decrease in the level of GIRK1 mRNA in ventricles was observed after Muscarinic acetylcholine receptors (mAChRs) stimulation at all time points (Fig. 1B)
Summary
Muscarinic acetylcholine receptors (mAChRs) couple to heterotrimeric G-proteins to regulate multiple effector molecules such as the GIRK family of inwardly rectifying Kϩ channels and the enzymes adenylyl cyclase and phospholipase C. Prolonged agonist exposure (hours) results in a decrease in mAChR number and recovery requires de novo protein synthesis (10 –12) Another consequence of continued mAChR activation is a decrease in transcription of mAChR genes. In chick heart, both m2 and m4 mAChR mRNA are decreased in a time- and dose-dependent manner [8]. This regulation of mAChR mRNA is dependent on both the activation of phospholipase C and the inhibition of adenylyl cyclase [13] These decreases in receptors at the cell surface and in gene expression result in a reduced physiological response to subsequent receptor stimulation. We determined the effects of mAChR activation in vivo on the expression of GIRK1 and GIRK4 mRNA and GIRK1 protein in chick atria and ventricles
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