Role of calcium in mediating the biphasic contraction of the rabbit urinary bladder

Abstract

1. 1. The response of the urinary bladder to field stimulation is biphasic in nature consisting of an initial phasic contraction followed by a prolonged tonic phase which lasts for the duration of the stimulation. 2. 2. The phasic response is mediated by the release of neurohumoral transmitters, primarily acetylcholine (via muscarinic receptor stimulation) and ATP (via purinergic receptor stimulation). The tonic component is mediated entirely via muscarinic receptor stimulation. 3. 3. The present study investigates the dependence on extracellular calcium of the phasic and tonic contractile responses to field stimulation, bethanechol, and ATP. The results can be summarized as follows: 4. 4. Field stimulation (2 and 32 Hz) and bethanechol evoke a biphasic contractile response whereas ATP evokes only a phasic response. 5. 5. There were no significant effects of either calcium channel blockers or calcium fee EGTA medium on either spontaneous contraction or basal tension of muscle strips. 6. 6. The calcium channel antagonists diltiazem and verapamil inhibited both the phasic and tonic responses induced by field stimulation (both 2 and 32 Hz) in a dose dependent manner. 7. 7. For both 2 and 32 Hz stimulation, the ED 50s for the inhibition of the tonic phases of the responses to field stimulation were significantly lower than the ED 50s for the inhibition of the phasic responses. 8. 8. The tonic phase of the responses to field stimulation were inhibited to a significantly greater degree than the phasic responses by incubation in calcium-free medium containing EGTA. 9. 9. Both the phasic and tonic components of the response to bethanechol stimulation were inhibited equally, and followed a similar time course as the tonic component of field stimulation. 10. 10. The response to ATP was relatively insensitive to calcium depletion. 11. 11. In summary, the tonic response to field stimulation (purely cholinergic) is significantly more dependent on extracellular calcium than is the phasic response (cholinergic + purinergic).