Differential susceptibility of cholinergic and noncholinergic neurogenic responses to calcium channel blockers and low Ca2+ medium in rat urinary bladder.

1. The influence of calcium channel blockers and low Ca2+ medium on the neurogenic responses to single pulse electric field stimulation in rat urinary bladder has been examined. 2. Single pulse stimulation evoked a biphasic contractile response consisting of a fast component with a time to peak of 0.72 +/- 0.05 s and a slow component that reached a maximal tension at 2.8 +/- 0.21 s, possibly mediated by two different neurotransmitters. 3. Atropine (3 x 10(-6) M) selectively inhibited the slow component without altering the fast component, suggesting the involvement of cholinergic and non-cholinergic neurotransmitters, respectively. 4. Reducing Ca2+ in the medium to 1/4 of the normal, abolished the slow component of the neurogenic response while the fast contractile response was not altered which may indicate a relatively greater dependence of the cholinergic component on extracellular Ca2+ than the noncholinergic one. 5. The IC50 values for the fast component with respect to verapamil and diltiazem were 1.08 microM and 1.76 microM, respectively. The greater susceptibility of the slow component to calcium channel blockers (IC50 values of verapamil: 0.07 microM and of diltiazem: 0.25 microM) indicates the differential activation of slow calcium channels by the endogenously released substances. 6. Calcium channel blockers inhibited the ATP-induced contraction which was comparable to that of the non-cholinergic component of the neurogenic response suggesting the involvement of ATP as a possible neurotransmitter. 7. Ach-induced contractions were relatively less susceptible to calcium channel blockers and low Ca2+ medium than was the atropine-sensitive cholinergic component of the neurogenic response.