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

1 Electrical held stimulations (EFS) of the opossum and canine lower oesoph ageal sphincters (OLOS and CLOS respectively) and opossum oesophageal body circular muscle (OOBCM) induce non-adrenergic, non-cholinergic (NANC) relax ations 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 isolat ed smooth muscle cells, we tested whether VIP acted through myogenic NO pro duction. 2 Outward currents were similar in OOBCM and OLOS and NO increased them reg ardless of pipette Ca-i(2+), from 50 - 8000 nM. L-NAME or L-NOARG did not b lock outward currents in OLOS at 200 nM pipette Ca23 Outward currents in CLOS cells decreased at 200 nM pipette Ca2+ or less b ut NO donors still increased them. VIP had no effect on outward currents in cells from OOBCM, OLOS or CLOS under conditions of pipette Ca2+ at which N O donors increased outward K+ currents. 4 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 an d inhibits contraction of OOBCM by a mechanism unrelated to release of myog enic NO or an increase in outward current. 5 Also, the different dependence of outward currents of OOBCM and OLOS on p ipette Ca2+ from those of CLOS suggests that different K+ channels are invo lved and that myogenic NO production contributes to K+ channel activity in CLOS but not in OLOS or OOBCM.