Activation of outward K + currents: effect of VIP in oesophagus

Electrical field stimulations (EFS) of the opossum and canine lower oesophageal sphincters (OLOS and CLOS respectively) and opossum oesophageal body circular muscle (OOBCM) induce non‐adrenergic, non‐cholinergic (NANC) relaxations of any active tension and NO‐mediated hyperpolarization. VIP relaxes the OLOS and CLOS and any tone in OOBCM without major electrophysiological effects. These relaxations are not blocked by NOS inhibitors. Using isolated smooth muscle cells, we tested whether VIP acted through myogenic NO production. Outward currents were similar in OOBCM and OLOS and NO increased them regardless of pipette Ca 2+ i , from 50–8000 n M . L ‐NAME or L ‐NOARG did not block outward currents in OLOS at 200 n M pipette Ca 2+ . Outward currents in CLOS cells decreased at 200 n M pipette Ca 2+ or less but NO donors still increased them. VIP had no effect on outward currents in cells from OOBCM, OLOS or CLOS under conditions of pipette Ca 2+ at which NO donors increased outward K + currents. We conclude, VIP does not mimic electrophysiological effects of NO donors on isolated cells of OOBCM, OLOS or CLOS. VIP relaxes the OLOS and CLOS and inhibits contraction of OOBCM by a mechanism unrelated to release of myogenic NO or an increase in outward current. Also, the different dependence of outward currents of OOBCM and OLOS on pipette Ca 2+ from those of CLOS suggests that different K + channels are involved and that myogenic NO production contributes to K + channel activity in CLOS but not in OLOS or OOBCM.British Journal of Pharmacology (1999) 127 , 553–561; doi: 10.1038/sj.bjp.0702579