Tumor necrosis factor-alpha inhibits the cardiac delayed rectifier K current via the asphingomyelin pathway. 2006

Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
Division of Cardiology, Niigata University Graduate School of Medical and Dental Science, Niigata, Japan.

Tumor necrosis factor-alpha (TNF-alpha) affects contractility and ionic currents in the heart. However, the electrophysiological effects, especially on delayed rectifier K currents (IK), have not yet been fully elucidated. We examined the effects of TNF-alpha on IK. Using a voltage-clamp method, IK was measured in guinea pig ventricular myocytes in the basal state and after pharmacological intervention. To specify the site of the action of TNF-alpha, the myocytes were incubated with pertussis toxin or N-oleoylethanolamine, a ceramidase inhibitor, and IK was measured. TNF-alpha suppressed IK when it was enhanced by isoproterenol, histamine or forskolin but not in the basal state or when IK was augmented by an internal application of cyclic AMP. Both pre-incubation with pertussis toxin and N-oleoylethanolamine abolished the inhibitory action of TNF-alpha on isoproterenol-augmented IK. TNF-alpha inhibits IK, mainly IKs, when it is augmented by PKA as a result of the generation of sphingosine.

UI MeSH Term Description Entries
D007545 Isoproterenol Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D009829 Oleic Acids A group of fatty acids that contain 18 carbon atoms and a double bond at the omega 9 carbon. Octadecenoic Acids,Acids, Octadecenoic,Acids, Oleic
D004983 Ethanolamines AMINO ALCOHOLS containing the ETHANOLAMINE; (-NH2CH2CHOH) group and its derivatives. Aminoethanols
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D000581 Amidohydrolases Any member of the class of enzymes that catalyze the cleavage of amide bonds and result in the addition of water to the resulting molecules. Amidases,Amidohydrolase
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013109 Sphingomyelins A class of sphingolipids found largely in the brain and other nervous tissue. They contain phosphocholine or phosphoethanolamine as their polar head group so therefore are the only sphingolipids classified as PHOSPHOLIPIDS. Sphingomyelin
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha
D051668 Delayed Rectifier Potassium Channels A group of slow opening and closing voltage-gated potassium channels. Because of their delayed activation kinetics they play an important role in controlling ACTION POTENTIAL duration. Delayed Rectifying Potassium Channels

Related Publications

Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
September 2008, Neuroreport,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
December 1998, Journal of molecular and cellular cardiology,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
November 1988, Biophysical journal,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
November 1991, The Journal of membrane biology,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
February 2006, Journal of neurophysiology,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
August 1993, Cardiovascular drugs and therapy,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
January 2012, Journal of neuroscience research,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
February 1998, Biochemical and biophysical research communications,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
February 2010, The Journal of pharmacology and experimental therapeutics,
Katsuharu Hatada, and Takashi Washizuka, and Minoru Horie, and Hiroshi Watanabe, and Fumio Yamashita, and Masaomi Chinushi, and Yoshifusa Aizawa
August 1997, Circulation research,
Copied contents to your clipboard!