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

1 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. 2 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 colonic myocytes. L ‐Methionine was the most selective and had little or no effect on other known K + conductances in colonic myocytes. 3 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. 4 Pretreatment of muscles with tetrodotoxin, N W ‐nitro‐ L ‐arginine or 1 H ‐[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. 5 Nitrergic responses to nerve stimulation were reduced by sulfur‐containing amino acids. 6 These 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