Sulfur-containing amino acids block stretch-dependent K+ channels and nitrergic responses in the murine colon

Authors


Department of Physiology and Cell Biology, University of Nevada School of Medicine, MS352, Reno, NV 89557, U.S.A. E-mail: sdk@physiology.unr.edu

Abstract

  • 1Efforts to determine the role of stretch-dependent K+ (SDK) channels in enteric inhibitory neural responses in gastrointestinal muscles are difficult due to a lack of blocking drugs for SDK channels.
  • 2SDK channels are blocked by sulfur-containing amino acids. These compounds reduced the open probability of SDK channels in on and off-cell patches of murine colonic myocytes. L-Methionine was the most selective and had little or no effect on other known K+ conductances in colonic myocytes.
  • 3Application of L-cysteine, L-methionine or DL-homocysteine depolarized intact muscles and enhanced spontaneous contractions. D-Stereoisomers of these amino acids were less effective than L-stereoisomers.
  • 4Pretreatment of muscles with tetrodotoxin, NW-nitro-L-arginine or 1H-[1,2,4] oxadiazolo [4,3-a] quinoxalin-1-one reduced the depolarization responses to these compounds, suggesting that spontaneous neural activity and release of NO tonically activates SDK channels.
  • 5Nitrergic responses to nerve stimulation were reduced by sulfur-containing amino acids.
  • 6These data suggest that nitrergic inhibitory junction potentials are mediated, in part, by activation of SDK channels in murine colonic muscles.

British Journal of Pharmacology (2005) 144, 1126–1137. doi:10.1038/sj.bjp.0706154

Ancillary