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

Biochemical and Biophysical Research Communications
Katsuharu HatadaYoshifusa Aizawa

Abstract

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.

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Citations

May 23, 2006·Biochemical and Biophysical Research Communications·Yasutaka TanabeYoshifusa Aizawa
Oct 22, 2008·Critical Care Medicine·Milan StenglMartin Matejovic
Jan 27, 2015·Journal of the American Heart Association·Qinmei XiongKui Hong
Dec 21, 2018·Journal of the American Heart Association·Pietro Enea LazzeriniMohamed Boutjdir
Jan 23, 2019·Frontiers in Physiology·Alessandra AlíAdemuyiwa S Aromolaran
Oct 20, 2020·Frontiers in Physiology·Mingxian ChenShenghua Zhou
Sep 19, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Kiran Haresh Kumar PatelFu Siong Ng

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