Nitric oxide activates glibenclamide-sensitive K+ channels in urinary bladder myocytes through a c-GMP-dependent mechanism

In the present investigation, we used standard patch clamp techniques to test whether nitric oxide (NO) generation has any role to play with either activation or inhibition of ATP-sensitive (K-ATP) channels in guinea-pig urinary bladder. We found that NO generation leads to activation of K-ATP channels through a cyclic guanosine monophosphate (c-GMP)-dependent protein kinase. 3-Morpholinosydnonimine (SIN, 100 muM) potentiated activation of an inward current in whole cell patch clamp experiments. Glibenclamide (10 muM) and IH[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 muM) inhibited the SIN-activated current. Both in cell-attached and in inside out patches, SIN (200 muM) potentiated K-ATP channel activity, and the increased channel activity in inside out patches was suppressed by glibenclamide (50 muM), ATP (1 mM) and (9s,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-l-oxo-9,12,-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6] benzodiazocine-10-carboxylic acid, methyl ester (KT-5823, 10 nM). 8-Br-cGMP (100 muM) increased the K-ATP channel activity in cell-attached patches, and this was suppressed by glibenclamide (50 muM). These results suggest that the NO-c-GMP-PKG pathway contributes to activation of K-ATP channels in guinea-pig urinary bladder myocytes. (C) 2004 Elsevier B.V. All rights reserved.