title: Sulfur-containing amino acids block stretch-dependent K+ channels and nitrergic responses in the murine colon.
abstract: 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 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. 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.
authors.affiliation: Department of Surgery, Seoul National University, College of Medicine, Seoul 110-744, Korea.
authors.forename: Kyu Joo
authors.initials: KJ
authors.lastname: Park
authors.forename: Salah A
authors.initials: SA
authors.lastname: Baker
authors.forename: Sang Yun
authors.initials: SY
authors.lastname: Cho
authors.forename: Kenton M
authors.initials: KM
authors.lastname: Sanders
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Koh
mesh_terms: D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D026602:Nitrergic Neurons / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology*; D013457:Sulfur Compounds / Q000494:pharmacology*
chemical_list: D000596:Amino Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013457:Sulfur Compounds