Novel Paradigms Governing β1 -Adrenergic Receptor Trafficking in Primary Adult Rat Cardiac Myocytes

Molecular Pharmacology
Mohammed M NoohSuleiman W Bahouth

Abstract

The β1-adrenergic receptor (β1-AR) is a major cardiac G protein-coupled receptor, which mediates cardiac actions of catecholamines and is involved in genesis and treatment of numerous cardiovascular disorders. In mammalian cells, catecholamines induce the internalization of the β1-AR into endosomes and their removal promotes the recycling of the endosomal β1-AR back to the plasma membrane; however, whether these redistributive processes occur in terminally differentiated cells is unknown. Compartmentalization of the β1-AR in response to β-agonists and antagonists was determined by confocal microscopy in primary adult rat ventricular myocytes (ARVMs), which are terminally differentiated myocytes with unique structures such as transverse tubules (T-tubules) and contractile sarcomeres. In unstimulated ARVMs, the fluorescently labeled β1-AR was expressed on the external membrane (the sarcolemma) of cardiomyocytes. Exposing ARVMs to isoproterenol redistributed surface β1-ARs into small (∼225-250 nm) regularly spaced internal punctate structures that overlapped with puncta stained by Di-8 ANEPPS, a membrane-impermeant T-tubule-specific dye. Replacing the β-agonist with the β-blocker alprenolol, induced the translocation of the wild-t...Continue Reading

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Jan 18, 2020·International Journal of Molecular Sciences·Sonia MaccariPaola Molinari
Jun 6, 2021·Proceedings of the National Academy of Sciences of the United States of America·Marc Bathe-PetersPaolo Annibale

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