title: Effects of modulators of AMP-activated protein kinase on TASK-1/3 and intracellular Ca(2+) concentration in rat carotid body glomus cells.
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.
authors: Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, United States. Electronic address: Donghee.kim@rosalindfranklin.edu.
authors: Donghee
authors: D
authors: Kim
authors: Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, United States; Department of Physiology and Institute of Health Sciences, Gyeongsang National University School of Medicine, 90 Chilam, Jinju 660-751, Republic of Korea.
authors: Dawon
authors: D
authors: Kang
authors: Department of Physiology and Biophysics, Chicago Medical School, Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064, United States.
authors: Elizabeth A
authors: EA
authors: Martin
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, 1 Children's Way, Little Rock, AR 72202, United States.
authors: Insook
authors: I
authors: Kim
authors: Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, 1 Children's Way, Little Rock, AR 72202, United States. Electronic address: carrolljohnl@uams.edu.
authors: John L
authors: JL
authors: Carroll
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds; D002118:Calcium / Q000378:metabolism*; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009419:Nerve Tissue Proteins; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D011753:Pyrones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012265:Ribonucleotides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology
chemical_list: D001713:Biphenyl Compounds; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; C498740:Kcnk5 protein, rat; C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D011753:Pyrones; D012265:Ribonucleotides; D013876:Thiophenes; C420132:potassium channel subfamily K member 3; D000620:Aminoimidazole Carboxamide; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; C512408:4-hydroxy-3-(4-(2-hydroxyphenyl)phenyl)-6-oxo-7H-thieno(2,3-b)pyridine-5-carbonitrile; D002118:Calcium
keywords: AMP kinase; Background K(+) channels; Carotid body; Chemoreceptors; Hypoxia