Lipopolysaccharides up-regulate Kir6.1/SUR2B channel expression and enhance vascular KATP channel activity via NF-kappaB-dependent signaling

J Biol Chem. 2010 Jan 29;285(5):3021-9. doi: 10.1074/jbc.M109.058313. Epub 2009 Dec 3.


Sepsis is a severe medical condition causing a large number of deaths worldwide. Recent studies indicate that the septic susceptibility is attributable to the vascular ATP-sensitive K(+) (K(ATP)) channel. However, the mechanisms underlying the channel modulation in sepsis are still unclear. Here we show evidence for the modulation of vascular K(ATP) channel by septic pathogen lipopolysaccharides (LPS). In isolated mesenteric arterial rings, phenylephrine (PE) produced concentration-dependent vasoconstriction that was relaxed by pinacidil, a selective K(ATP) channel opener. The PE response was disrupted with a LPS treatment. In acutely dissociated aortic smooth myocytes the LPS treatment augmented K(ATP) channel activity, and hyperpolarized the cells. Quantitative PCR analysis showed that LPS raised Kir6.1 and SUR2B transcripts in a concentration-dependent manner, which was suppressed by transcriptional inhibition. Consistently, the same LPS treatment did not affect Kir6.1/SUR2B channels in a heterologous expression system. The LPS effect on Kir6.1 and SUR2B expression was abolished in the presence of NF-kappaB inhibitors. Several other Toll-like receptor ligands also stimulated Kir6.1 and SUR2B expression to a similar degree as LPS. Thus, the effect of LPS on vasodilation involves up-regulation of K(ATP) channel expression, in which the NF-kappaB-dependent signaling plays an important role.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / pathology
  • Dose-Response Relationship, Drug
  • Humans
  • KATP Channels / metabolism*
  • Lipopolysaccharides / chemistry
  • Lipopolysaccharides / metabolism*
  • Muscle, Smooth / pathology
  • NF-kappa B / metabolism*
  • Phenylephrine / metabolism
  • Pinacidil / pharmacology
  • Potassium Channels, Inwardly Rectifying / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Up-Regulation*
  • Vasodilator Agents / pharmacology


  • KATP Channels
  • Lipopolysaccharides
  • NF-kappa B
  • Potassium Channels, Inwardly Rectifying
  • Vasodilator Agents
  • uK-ATP-1 potassium channel
  • Phenylephrine
  • Pinacidil