Abstract
Acute hypoxia depolarizes carotid body chemoreceptor (glomus) cells and elevates intracellular Ca(2+) concentration ([Ca(2+)]i). Recent studies suggest that AMP-activated protein kinase (AMPK) mediates these effects of hypoxia by inhibiting the background K(+) channels such as TASK. Here we studied the effects of modulators of AMPK on TASK activity in cell-attached patches. Activators of AMPK (1mM AICAR and 0.1-0.5mM A769662) did not inhibit TASK activity or cause depolarization during acute (10min) or prolonged (2-3h) exposure. Hypoxia inhibited TASK activity by ∼70% in cells pretreated with AICAR or A769662. Both AICAR and A769662 (15-40min) failed to increase [Ca(2+)]i in glomus cells. Compound C (40μM), an inhibitor of AMPK, showed no effect on hypoxia-induced inhibition of TASK. AICAR and A769662 phosphorylated AMPKα in PC12 cells, and Compound C blocked the phosphorylation. Our results suggest that AMPK does not affect TASK activity and is not involved in hypoxia-induced elevation of intracellular [Ca(2+)] in isolated rat carotid body glomus cells.
Keywords:
AMP kinase; Background K(+) channels; Carotid body; Chemoreceptors; Hypoxia.
Copyright © 2014 Elsevier B.V. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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AMP-Activated Protein Kinases / antagonists & inhibitors
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AMP-Activated Protein Kinases / metabolism*
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Aminoimidazole Carboxamide / analogs & derivatives
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Aminoimidazole Carboxamide / pharmacology
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Animals
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Biphenyl Compounds
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Calcium / metabolism*
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Carotid Body / cytology
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Carotid Body / drug effects
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Carotid Body / physiology*
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Enzyme Activators / pharmacology
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Enzyme Inhibitors / pharmacology
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Hypoxia / physiopathology
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Intracellular Space / drug effects
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Intracellular Space / metabolism
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Membrane Potentials / drug effects
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Membrane Potentials / physiology
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Nerve Tissue Proteins
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PC12 Cells
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Patch-Clamp Techniques
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Phosphorylation / drug effects
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Potassium Channels, Tandem Pore Domain / metabolism*
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Pyrones / pharmacology
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Rats
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Rats, Sprague-Dawley
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Ribonucleotides / pharmacology
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Thiophenes / pharmacology
Substances
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Biphenyl Compounds
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Enzyme Activators
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Enzyme Inhibitors
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Kcnk5 protein, rat
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Kcnk9 protein, rat
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Nerve Tissue Proteins
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Potassium Channels, Tandem Pore Domain
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Pyrones
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Ribonucleotides
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Thiophenes
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potassium channel subfamily K member 3
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Aminoimidazole Carboxamide
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AMP-Activated Protein Kinases
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AICA ribonucleotide
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4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile
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Calcium