Brief Article
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World J Gastroenterol. Dec 14, 2010; 16(46): 5852-5860
Published online Dec 14, 2010. doi: 10.3748/wjg.v16.i46.5852
Nitric oxide activation of a potassium channel (BKCa) in feline lower esophageal sphincter
Marie-Claude L’Heureux, Ahmad Muinuddin, Herbert Y Gaisano, Nicholas E Diamant
Marie-Claude L’Heureux, Ahmad Muinuddin, Herbert Y Gaisano, Nicholas E Diamant, Department of Physiology, University of Toronto, Toronto, Ontario, M5T 1A8, Canada
Marie-Claude L’Heureux, Ahmad Muinuddin, Nicholas E Diamant, Toronto Western Research Institute, University Health Network, Toronto, Ontario, M5T 2S8, Canada
Ahmad Muinuddin, Herbert Y Gaisano, Nicholas E Diamant, Department of Medicine, University of Toronto, Toronto, Ontario, M5S 1A8, Canada
Author contributions: L’Leureux MC and Muinuddin A were involved in hypothesis development, performed all experiments, data analysis and wrote the initial manuscript; Gaisano HY and Diamant NE were involved in hypothesis development, supervision of the research study as well as manuscript revision.
Supported by A Postgraduate Fellowship Award to L’Heureux MC from the Department of Medicine, University of Toronto as well as a doctoral research studentship and an Operating Grant from the Canadian Institutes of Health Research (Gaisano HY and Diamant NE)
Correspondence to: Dr. Nicholas E Diamant, Toronto Western Research Institute, University Health Network, 8th Floor, Main Pavillion Rm 327, 399 Bathurst Street, Toronto, Ontario M5T 2S8, Canada. ndiamant@sympatico.ca
Telephone: +1-416-6035746 Fax: +1-416-6036204
Received: May 14, 2010
Revised: July 13, 2010
Accepted: July 20, 2010
Published online: December 14, 2010
Abstract

AIM: To assess the effect of nitric oxide (NO) on the large conductance potassium channel (BKCa) 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 ± 0.8mV 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 BKCa 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 BKCa 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.

CONCLUSION: Exogenous NO activates BKCa only in CM of the cat. However, as opposed to other species, exogenous NO-induced relaxation is predominantly by a non-BKCa mechanism, and endogenous NO has minimal effect on resting tone.

Keywords: Circular smooth muscle; Feline; K+ channel; Lower esophageal sphincter; Nitric oxide; Sling; Tone