Oscillatory membrane currents paradoxically induced via NO-activated pathways in detrusor cells.
Oscillatory inward membrane currents (I(oscil-in)) reflecting intracellular Ca(2+) ([Ca(2+)](i)) activity in detrusor cells, are thought to play an important role in producing tonic bladder contractions during micturition. The present patch clamp study revealed a new activation mechanism: sodium nitroprusside (SNP), a nitric oxide (NO) donor induced I(oscil-in) in a subpopulation of detrusor cells. The inhibitory effect of niflumic acid on SNP-induced I(oscil-in) suggests that Ca(2+)-activated Cl(-) channels are responsible for this current. In addition, SNP-induced I(oscil-in) required the cooperation of Ca(2+) influx through SK&F96365-sensitive channels and intracellular Ca(2+) release channels sensitive to ryanodine but insensitive to xestospongin C (XeC). This is also true for muscarinic agonist (carbachol: CCh)-induced I(oscil-in). However, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylyl cyclase inhibitor, suppressed SNP-induced I(oscil-in) but not CCh-induced I(oscil-in). The results suggest that a subpopulation of detrusor cells employ the NO/cGMP cascade to potentiate bladder contraction. Mechanisms underlying NO-induced I(oscil-in) are likely to contribute not only to the physiology but also to the pathophysiology of the lower urinary tract.
Kajioka
Shunichi
S
University Department of Pharmacology, Mansfield Road, Oxford OX1 3QT, UK.
Nakayama
Shinsuke
S
Seki
Narihito
N
Naito
Seiji
S
Brading
Alison F
AF
D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D002450:Cell Communication; D006152:Cyclic GMP / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013552:Swine; D001743:Urinary Bladder / Q000502:physiology*
D002316:Cardiotonic Agents; D020030:Nitric Oxide Donors; D010069:Oxadiazoles; D019837:Ryanodine Receptor Calcium Release Channel; D009599:Nitroprusside; D009569:Nitric Oxide; D002217:Carbachol; D006162:Guanylate Cyclase; D006152:Cyclic GMP