Inhibition of PDE4 with rolipram enhances endogenous Kv7.5 current in A7r5 cells in a PKA-dependent manner. (A) Current-voltage (I-V) relationships of endogenous Kv7.5 currents recorded in A7r5 cells before (control, solid circles) and during treatment with increasing concentrations of rolipram (open symbols: circle, 1 nM; triangle, 10 nM; reversed triangle, 30 nM; square, 100 nM; and diamond, 1 μM). (B) Cumulative rolipram dose-response curve for Kv7.5 current enhancement, presented as fold increase in amplitude of current recorded at −20 mV, fitted to the Hill equation [n = 4–5, * indicates significant difference from control, P < 0.001, one-way repeated-measures analysis of variance (ANOVA)]. (C and D) I-V relationships of Kv7.5 currents recorded in A7r5 cells before (control, solid circles), after 30 minutes of pretreatment with either vehicle for KT5720 (0.01% dimethylsulfoxide, solid triangles) (C) or 1 μM KT5720 (D), and after 5 minutes of treatment with 100 nM rolipram (open circles). Currents were normalized to currents recorded at −20 mV before application of rolipram (n = 4, * indicates significant difference from control, P < 0.05, one-way repeated-measures ANOVA).