PMID- 17337591
OWN - NLM
STAT- MEDLINE
DCOM- 20070912
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 293
IP  - 1
DP  - 2007 Jul
TI  - TNF-alpha downregulates transient outward potassium current in rat ventricular 
      myocytes through iNOS overexpression and oxidant species generation.
PG  - H238-45
AB  - Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that has 
      been implicated in the pathogenesis of heart failure. Prolongation of the action 
      potential duration and downregulation of several K(+) currents might participate 
      in the genesis of arrhythmias associated with chronic heart failure. Little 
      information is available related to the mechanism by which TNF-alpha modulates 
      cardiac K(+) channels. The present study analyzes the effect of TNF-alpha on the 
      transient outward K(+) current (I(to)) in rat ventricular myocytes, using the 
      whole cell patch-clamp technique. We found that TNF-alpha is able to induce a 
      significant reduction of I(to) density, modifies its inactivation, and 
      downregulates the Kv4.2 protein expression, while calcium current density is not 
      affected. We have also demonstrated that the reduction of I(to) density induced 
      by TNF-alpha was prevented by the selective inducible nitric oxide synthase 
      (iNOS) inhibitor 1400-W, the protein synthesis inhibitor cycloheximide, the 
      antioxidant tocopherol, and the superoxide dismutase mimetic manganese(III) 
      tetrakis (4-benzoic acid) porphyrin. In addition, a reduced I(to) density was 
      recorded in ventricular myocytes exposed to peroxynitrite, supporting a possible 
      participation of this oxidant in the effects of TNF-alpha on I(to). We conclude 
      that TNF-alpha exposure, through iNOS induction and generation of oxidant 
      species, promotes electrophysiological changes (decreased I(to) and action 
      potential duration prolongation) in rat ventricular myocytes, providing new 
      insights into how cytokines modulate K(+) channels in the heart.
FAU - Fernandez-Velasco, Maria
AU  - Fernandez-Velasco M
AD  - Institute of Pharmacology and Toxicology, CSIC-UCM School of Medicine, 
      Universidad Complutense, 28040 Madrid, Spain.
FAU - Ruiz-Hurtado, Gema
AU  - Ruiz-Hurtado G
FAU - Hurtado, Olivia
AU  - Hurtado O
FAU - Moro, Maria Angeles
AU  - Moro MA
FAU - Delgado, Carmen
AU  - Delgado C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070302
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Heart Ventricles/cytology/*metabolism
MH  - Male
MH  - Membrane Potentials/*physiology
MH  - Myocytes, Cardiac/*metabolism
MH  - Nitric Oxide Synthase Type II/*metabolism
MH  - Potassium/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/*metabolism
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Up-Regulation/physiology
EDAT- 2007/03/06 09:00
MHDA- 2007/09/13 09:00
CRDT- 2007/03/06 09:00
PHST- 2007/03/06 09:00 [pubmed]
PHST- 2007/09/13 09:00 [medline]
PHST- 2007/03/06 09:00 [entrez]
AID - 01122.2006 [pii]
AID - 10.1152/ajpheart.01122.2006 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H238-45. doi: 
      10.1152/ajpheart.01122.2006. Epub 2007 Mar 2.