title: Nitric oxide activation of a potassium channel (BK(Ca)) in feline lower esophageal sphincter.
abstract: OBJECTIVE
  To assess the effect of nitric oxide (NO) on the large conductance potassium channel (BK(Ca)) in isolated circular (CM) and sling (SM) muscle cells and muscle strips from the cat lower esophageal sphincter (LES) to determine its regulation of resting tone and relaxation.
  
  
  METHODS
  Freshly enzymatically-digested and isolated circular smooth muscle cells were prepared from each LES region. To study outward K+ currents, the perforated patch clamp technique was employed. To assess LES resting tone and relaxation, muscle strips were mounted in perfused organ baths.
  
  
  RESULTS
  (1) Electrophysiological recordings from isolated cells: (a) CM was more depolarized than SM (-39.7 ± 0.8 mV vs -48.1 ± 1.6 mV, P < 0.001), and maximal outward current was similar (27.1 ± 1.5 pA/pF vs 25.7 ± 2.0 pA/pF, P > 0.05); (b) The NO donor sodium nitroprusside (SNP) increased outward currents only in CM (25.9 ± 1.9 to 46.7 ± 4.2 pA/pF, P < 0.001) but not SM (23.2 ± 3.1 to 27.0 ± 3.4 pA/pF, P > 0.05); (c) SNP added in the presence of the BK(Ca) antagonist iberiotoxin (IbTX) produced no increase in the outward current in CM (17.0 ± 2.8 vs 13.7 ± 2.2, P > 0.05); and (d) L-NNA caused a small insignificant inhibition of outward K+ currents in both muscles; and (2) Muscle strip studies: (a) Blockade of the nerves with tetrodotoxin (TTX), or BK(Ca) with IbTX had no significant effect on resting tone of either muscle; and (b) SNP reduced tone in both muscles, and was unaffected by the presence of TTX or IbTX.
  
  
  CONCLUSIONS
  Exogenous NO activates BK(Ca) only in CM of the cat. However, as opposed to other species, exogenous NO-induced relaxation is predominantly by a non-BK(Ca) mechanism, and endogenous NO has minimal effect on resting tone.
authors.affiliation: Toronto Western Research Institute, University Health Network, 8th Floor, Main Pavillion Rm 327, 399 Bathurst Street, Toronto, Ontario M5T2S8, Canada.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: L'Heureux
authors.forename: Ahmad
authors.initials: A
authors.lastname: Muinuddin
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.forename: Nicholas E
authors.initials: NE
authors.lastname: Diamant
mesh_terms: D000818:Animals; D002415:Cats; D049630:Esophageal Sphincter, Lower / Q000187:drug effects / Q000502:physiology*; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D051036:Large-Conductance Calcium-Activated Potassium Channels; D020030:Nitric Oxide Donors; D010455:Peptides; D026941:Sodium Channel Blockers; D009599:Nitroprusside; D009569:Nitric Oxide; D013779:Tetrodotoxin; C064719:iberiotoxin