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

Abstract

Efforts 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. SDK 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 colonie myocytes. L-Methionine was the most selective and had little or no effect on other known K + conductances in colonic myocytes. Application 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. Pretreatment of muscles with tetrodotoxin, N W-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. Nitrergic responses to nerve stimulation were reduced by sulfur-containing amino acids. These data suggest that nitrergic inhibitory junction potentials are mediated, in part, by activation of SDK channels in murine colonic muscles. © 2005 Nature Publishing Group All rights reserved.