Field stimulation responses of rat urinary bladder detrusor smooth-muscle. Dependence upon slow calcium channel activity determined by K+ depolarization and calcium antagonists.

Field stimulation responses of rat urinary bladder detrusor smooth muscle were unaffected by atropine, phentolamine, propranolol, caffeine and theophylline. After caffeine or theophylline treatment, previously quiescent detrusor preparations developed pronounced spontaneous contractile activity. Both natural spontaneous contractile activity and field stimulation responses were eliminated in Ca-free EGTA media. After washout, both kinds of activity returned but over quite different time scales. At moderate levels of K+-induced depolarization which inactivate fast Ca-channels, field stimulation responses persisted and additively superimposed upon the K+-induced tension, suggesting that field stimulation-induced depolarization had activated slow voltage-dependent Ca-channels. Almost 61% of detrusor muscle preparations examined showed some spontaneous contractile activity. Such preparations were more sensitive to K+-induced depolarization than quiescent preparations and K+-depolarization greatly accelerated the spontaneous activity of these muscle strips. The slow Ca-channel blockers nifedipine and verapamil eliminated field stimulation responses in the 10(-6)-10(-5) M range, but octylonium bromide was far less effective even at 10(-4) M. The inorganic Ca-channel blocker Mn2+ inhibited field stimulation responses at 0.5-1.0 mM but La3+ was surprisingly far less effective than Mn2+ in this concentration range, requiring a 1 mM level to achieve a 50% inhibition of response. It is concluded that field stimulation induced a depolarization of rat urinary bladder detrusor muscle which activates slow voltage-dependent Ca-channels. Field stimulation responses and natural spontaneous activity appear to strongly depend upon a sustained Ca influx through these channels for the sustained release of intracellular calcium and the maintenance of contractile force.