NDLI: HL-1 cells express an inwardly rectifying $K^{+}$ current activated via muscarinic receptors comparable to that in mouse atrial myocytes

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Nobles, Muriel Sebastian, Sonia Tinker, Andrew
Description	Country affiliation: United kingdom Author Affiliation: Nobles M ( Department of Medicine, BHF Laboratories, University College London, The Rayne Institute, 5 University Street, London, WC1E 6JJ, UK.)
Abstract	An inwardly rectifying K(+) current is present in atrial cardiac myocytes that is activated by acetylcholine (I(KACh)). Physiologically, activation of the current in the SA node is important in slowing the heart rate with increased parasympathetic tone. It is a paradigm for the direct regulation of signaling effectors by the Gbetagamma G-protein subunit. Many questions have been addressed in heterologous expression systems with less focus on the behaviour in native myocytes partly because of the technical difficulties in undertaking comparable studies in native cells. In this study, we characterise a potassium current in the atrial-derived cell line HL-1. Using an electrophysiological approach, we compare the characteristics of the potassium current with those in native atrial cells and in a HEK cell line expressing the cloned Kir3.1/3.4 channel. The potassium current recorded in HL-1 is inwardly rectifying and activated by the muscarinic agonist carbachol. Carbachol-activated currents were inhibited by pertussis toxin and tertiapin-Q. The basal current was time-dependently increased when GTP was substituted in the patch-clamp pipette by the non-hydrolysable analogue GTPgammaS. We compared the kinetics of current modulation in HL-1 with those of freshly isolated atrial mouse cardiomyocytes. The current activation and deactivation kinetics in HL-1 cells are comparable to those measured in atrial cardiomyocytes. Using immunofluorescence, we found GIRK4 at the membrane in HL-1 cells. Real-time RT-PCR confirms the presence of mRNA for the main G-protein subunits, as well as for M2 muscarinic and A1 adenosine receptors. The data suggest HL-1 cells are a good model to study IKAch.
File Format	HTM / HTML
ISSN	00316768
e-ISSN	14322013
DOI	10.1007/s00424-010-0799-z
Journal	Pflügers Archiv - European Journal of Physiology
Issue Number	1
Volume Number	460
Language	English
Publisher	Springer
Publisher Date	2010-06-01
Publisher Place	Germany
Access Restriction	Open
Subject Keyword	Discipline Physiology Acetylcholine Metabolism Ion Channel Gating Myocytes, Cardiac Potassium Channels, Inwardly Rectifying Potassium Receptor, Muscarinic M2 Animals Bee Venoms Pharmacology Carbachol Cell Line Cholinergic Agonists Fluorescent Antibody Technique G Protein-coupled Inwardly-rectifying Potassium Channels Guanosine 5'-o-(3-thiotriphosphate) Heart Atria Drug Effects Kinetics Mice Patch-clamp Techniques Pertussis Toxin Potassium Channel Blockers Antagonists & Inhibitors Genetics Rna, Messenger Reverse Transcriptase Polymerase Chain Reaction Transfection Comparative Study Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Physiology Physiology (medical) Clinical Biochemistry

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