Oscillatory membrane currents paradoxically induced via NO-activated pathways in detrusor cells

SummaryOscillatory inward membrane currents (Ioscil-in) reflecting intracellular Ca2+ ([Ca2+]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 Ioscil-in in a subpopulation of detrusor cells. The inhibitory effect of niflumic acid on SNP-induced Ioscil-in suggests that Ca2+-activated Cl− channels are responsible for this current. In addition, SNP-induced Ioscil-in required the cooperation of Ca2+ influx through SK&F96365-sensitive channels and intracellular Ca2+ release channels sensitive to ryanodine but insensitive to xestospongin C (XeC). This is also true for muscarinic agonist (carbachol: CCh)-induced Ioscil-in. However, 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a guanylyl cyclase inhibitor, suppressed SNP-induced Ioscil-in but not CCh-induced Ioscil-in. The results suggest that a subpopulation of detrusor cells employ the NO/cGMP cascade to potentiate bladder contraction. Mechanisms underlying NO-induced Ioscil-in are likely to contribute not only to the physiology but also to the pathophysiology of the lower urinary tract.