Molecular analysis of ATP-sensitive K(+) channel subunits expressed in mouse portal vein

Vascul Pharmacol. 2015 Dec:75:29-39. doi: 10.1016/j.vph.2015.06.018. Epub 2015 Jul 8.

Abstract

Background: Several combinations of inwardly rectifying K(+) channel 6.x family pore-forming (KIR6.x) subunits associated with sulphonylurea receptor (SUR.x) subunits have been detected among ATP-sensitive K(+) (KATP) channels. It remains to be established which of these is expressed in native vascular smooth muscle.

Methods: Pharmacological and electrophysiological properties of KATP channels in mouse portal vein were investigated using tension measurements and patch-clamp techniques. Molecular biological analyses were also performed to investigate the structural properties of these channels.

Results: Spontaneous contractions in mouse portal vein were reversibly reduced by pinacidil and MCC-134, and the pinacidil-induced relaxation was antagonized by glibenclamide and U-37883A. In cell-attached mode, pinacidil activated glibenclamide-sensitive K(+) channels with a conductance (35 pS) similar to that of KIR6.1. RT-PCR analysis revealed the expression of KIR6.1, KIR6.2 and SUR2B transcripts. Using real-time PCR methods, the quantitative expression of KIR6.1 was much greater than that of KIR6.2. Immunohistochemical studies indicated the presence of KIR6.1 and SUR2B proteins in the smooth muscle layers of mouse portal vein and in single smooth muscle cells dispersed from mouse portal vein.

Conclusions: The results indicate that native KATP channels in mouse portal vein are likely to be composed of a heterocomplex of KIR6.1 and SUR2B subunits.

Keywords: ATP-sensitive K(+) channels; K(IR)6.1; SUR2B; Vascular smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / pharmacology
  • Animals
  • Glyburide / pharmacology
  • Imidazoles / pharmacology
  • KATP Channels / physiology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Morpholines / pharmacology
  • Muscle, Smooth, Vascular / metabolism*
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / metabolism
  • Patch-Clamp Techniques
  • Pinacidil / pharmacology
  • Portal Vein / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Sulfonylurea Receptors / metabolism*
  • Thioamides / pharmacology

Substances

  • Imidazoles
  • KATP Channels
  • MCC 134
  • Morpholines
  • Sulfonylurea Receptors
  • Thioamides
  • U 37883A
  • Pinacidil
  • Adamantane
  • Glyburide