Figure 5.
Modulation of IRKC by the cAMP–PKA signaling pathway. Inhibition of PKA activity with H8 (20 μm) suppressed the IRKC amplitude (A), whereas stimulation of PKA activity with cBIMP (25 μm) enhanced IRKC amplitude (B). C, Intracellular dialysis of the PKA inhibitor PKI (1 U/ml in pipette solution) into the cell inhibited IRKC amplitude (20 ± 4%; n = 4) 3 min after rupture of the membrane. D, Perfusion of the protein phosphatase inhibitor okadaic acid (10 μm) enhanced IRKC amplitude. E, Inhibition of basal PKA activities (20 μm H8) suppressed the amplitude of IRKC. Further activation of D1R [0.1 μm SKF 81297 (SKF)] induced an additive inhibition, suggesting a PKA-independent mechanism underlying the D1R-mediated inhibition of IRKC. F, Summary of the modulation of IRKC by the cAMP–PKA pathway. IRKC was enhanced by 23 ± 7% (n = 5) in the presence of cBIMP (25 μm) and by 15 ± 6% (n = 5) when tested with okadaic acid (10 μm). In contrast, H8 (20 μm) suppressed the amplitude of IRKC by 17 ± 6% (n = 5). Cnl, Control.