Neuregulin-1 suppresses muscarinic receptor expression and acetylcholine-activated muscarinic K+ channels in cardiac myocytes.
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.
Ford
Byron D
BD
Department of Anatomy and Neurobiology, Morehouse School of Medicine, 720 Westview Drive, SW, MRC 223, Atlanta, GA 30310, USA. BFord@msm.edu
Liu
Yun
Y
Mann
Mary Anne
MA
Krauss
Raul
R
Phillips
Kiwita
K
Gan
Li
L
Fischbach
Gerald D
GD
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
D020890:Neuregulin-1; D015221:Potassium Channels; D043588:Receptor, Muscarinic M4; D011976:Receptors, Muscarinic; D000109:Acetylcholine