Stimulation of Voltage-Dependent Contractions by Calcium Channel Activator Bay K 8644 in the Human Upper Urinary Tract in Vitro

Abstract

The effects of calcium agonist Bay K 8644 on mechanical activity were studied in isolated preparations of the human upper urinary tract. Bay K 8644 increased the amplitude of phasic-rhythmic contractions in calyceal segments in a concentration-dependent way. In inactive and unstimulated ureteral muscle strips, Bay K 8644 did not induce contractions. After depolarization of ureteral segments with an extracellular potassium concentration of 48mmol./l., Bay K 8644 produced a concentration-dependent increase of contractile force and enhanced phasic-rhythmic activity. The EC50 of the drug was 7.23 × 108mol./l. The potassium and calcium concentration-response-curves were shifted to the left and the maximum force development was increased. Tonic contractions induced by norepinephrine in calyceal and pelvic segments were not affected by Bay K 8644, but the tendency for phasic-rhythmic activity was increased. In contrast to calcium-antagonistic dihydropyridines like nifedipine, the dihydropyridine derivative Bay K 8644 displayed completely opposite effects, which are obviously limited to voltage-induced activation. These observations can be explained by assuming that these agents act at sites that are components or are associated with voltage-controlled calcium channels. Occupation of these sites may either increase (Bay K 8644) or decrease (nifedipine) the transmembrane calcium flux into the cell.