title: Neuregulin-1 suppresses muscarinic receptor expression and acetylcholine-activated muscarinic K+ channels in cardiac myocytes.
abstract: The neuregulin-1 family of growth factors regulates nicotinic acetylcholine receptor synthesis in skeletal muscle, but its role in cardiac myogenesis remains unclear. Here, we investigate the involvement of neuregulins in the development of cardiac cholinergic responsiveness. Treatment of chick cardiac myocytes with neuregulin-1 inhibited mRNA expression of the M4 muscarinic receptor, but not the M2 receptor. In addition, mRNA levels of GIRK1 were reduced in myocytes by treatment with neuregulin-1. Activation of cholinergic receptors in cultured chick atrial myocytes by carbachol produced an outward potassium current (I(K(ACh))), which was attenuated by 24-48-h pre-treatment with neuregulin-1. These data suggest that neuregulins can regulate cardiac parasympathetic tone and may be involved in the pathogenesis of cardiac arrhythmias and heart failure.
authors.affiliation: Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA. BFord@msm.edu
authors.forename: Byron D
authors.initials: BD
authors.lastname: Ford
authors.forename: Yun
authors.initials: Y
authors.lastname: Liu
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Mann
authors.forename: Raul
authors.initials: R
authors.lastname: Krauss
authors.forename: Kiwita
authors.initials: K
authors.lastname: Phillips
authors.forename: Li
authors.initials: L
authors.lastname: Gan
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Fischbach
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D020890:Neuregulin-1 / Q000502:physiology*; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D020890:Neuregulin-1; D015221:Potassium Channels; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D000109:Acetylcholine