Bradykinin inhibits the transient outward K+current in mouse Schwann cells via the cAMP/PKA pathway

Abstract

Bradykinin (BK) is an endogenous peptide with diverse biological actions and is considered to be an important mediator of the inflammatory response in both the peripheral and the central nervous systems. BK has attracted recent interest as a potential mediator of K+conductance, Cl−channels, and Ca2+-activated K+channels. However, few reports have associated BK with the voltage-gated K+current. In this study, we demonstrated that BK suppressed the transient outward potassium current ( IA) in mouse Schwann cells using whole cell recording techniques. At a concentration of 0.1 μM to 5 μM, BK reversibly inhibited IAin a dose-dependent manner with the modulation of steady-state activation and inactivation properties. The effect of BK on IAcurrent was abolished after preincubation with a B2receptor antagonist but could not be eliminated by B1receptor antagonist. Intracellular application of GTP-γS induced an irreversible decrease in IA, and the inhibition of Gsusing NF449 provoked a gradual augmentation in IAand eliminated the BK-induced effect on IA,while the Gi/oantagonist NF023 did not. The application of forskolin or dibutyryl-cAMP mimicked the inhibitory effect of BK on IAand abolished the BK-induced effect on IA. H-89, an inhibitor of PKA, augmented IAamplitude and completely eliminated the BK-induced inhibitory effect on IA. In contrast, activation of PKC by PMA augmented IAamplitude. A cAMP assay revealed that BK significantly increased intracellular cAMP level. It is therefore concluded that BK inhibits the IAcurrent in Schwann cells by cAMP/PKA-dependent pathways via activation of the B2receptor.