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 (KATP) channels in guinea-pig urinary bladder. We found that NO generation leads to activation of KATP channels through a cyclic guanosine monophosphate (c-GMP)-dependent protein kinase. 3-Morpholinosydnonimine (SIN, 100 microM) potentiated activation of an inward current in whole cell patch clamp experiments. Glibenclamide (10 microM) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ, 10 microM) inhibited the SIN-activated current. Both in cell-attached and in inside out patches, SIN (200 microM) potentiated KATP channel activity, and the increased channel activity in inside out patches was suppressed by glibenclamide (50 microM), ATP (1 mM) and (9s,10R,12R)-2,3,9,10,11,12-Hexahydro-10-methoxy-2,9-dimethyl-1-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 microM) increased the KATP channel activity in cell-attached patches, and this was suppressed by glibenclamide (50 microM). These results suggest that the NO-c-GMP-PKG pathway contributes to activation of K(ATP) channels in guinea-pig urinary bladder myocytes.
Deka
Dilip K
DK
University Department of Pharmacology, Mansfield Road, Oxford, OX1 3QT, UK.
Brading
Alison F
AF
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D015640:Ion Channel Gating / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008981:Molsidomine / Q000031:analogs & derivatives*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D020030:Nitric Oxide Donors; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D015398:Signal Transduction; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism*
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D002227:Carbazoles; D007211:Indoles; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D015221:Potassium Channels; D011810:Quinoxalines; C073601:KT 5823; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; C002385:linsidomine; D000255:Adenosine Triphosphate; D008981:Molsidomine; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D005905:Glyburide