MODULATION OF THE CYTOPLASMIC CA2+-CONCENTRATION IN ISOLATED MYOCYTES OF THE BLADDERS BY ANTICHOLINERGIC AGENTS

The increased smooth muscle tone in the spastic bladder is based on an enhanced acetylcholine release and is mediated by cholinergic receptors. The present study was designed to compare on the cellular level the anticholinergic potency of oxybutynin and trospiumchloride by using the patch-clamp technique the Ca2+-sensitive fluorescence dye FURA II. Bath application of acetylcholine induced a dose-dependent increase of the free cytoplasmic Ca2+-concentration [Ca2+](i) by stimulation of voltage-dependent Ca2+-channel current (I-Ca). The cholinergic receptor blockers trospiumchloride EC(50)=43+/-12 nM (n=46), oxybutynin EC(50)=890+/-60 nM, n=32) completely blocked the acetylcholine induced I-Ca stimulation in a dose-dependent manner. The trospiumchloride induced inhibition of the stimulated I-Ca could not be reversed within 300 min suggesting al long-term binding with high affinity of trospiumchloride to bladder smooth muscle cholinergic receptors. Moreover trospiumchloride and oxybutynin inhibited the basal, e.g. the nonstimulated I-Ca indicating the involvement of smooth muscle relaxing mechanisms independent from cholinergic receptor blockade.