The Adenylyl Cyclase Inhibitor MDL-12,330A Potentiates Insulin Secretion via Blockade of Voltage-Dependent K+ Channels in Pancreatic Beta Cells
Figure 4
MDL-12,330A inhibits KV currents in a dose-dependent manner in rat beta cells.
A. representative time-response curve of KV currents in response to 400 ms voltage steps to +70 mV in the absence and presence of 1, 5, 10, 15 and 30 µM MDL-12,330A (MDL) in the same cell. The holding potential was −70 mV and voltage steps were applied every 3 s in perforated whole-cell configuration. The addition of MDL-12,330A is indicated by the bar with the specific concentrations. B. plot of the fraction of control current blocked (Fraction Blocked) versus MDL-12,330A concentration for all cells tested (n = 5). The continuous line is a fit of the four-parameter logistic equation to the data. Parameters of the fit are: IC50 = 7.22 µM. C and D. representative time-response scatterplot of KV currents in the absence and presence of H89 (n = 7) and ESI-09 (ESI, n = 7).