title: 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 Ca(2+)-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 (I(A)) in mouse Schwann cells using whole cell recording techniques. At a concentration of 0.1 muM to 5 muM, BK reversibly inhibited I(A) in a dose-dependent manner with the modulation of steady-state activation and inactivation properties. The effect of BK on I(A) current was abolished after preincubation with a B(2) receptor antagonist but could not be eliminated by B(1) receptor antagonist. Intracellular application of GTP-gammaS induced an irreversible decrease in I(A), and the inhibition of G(s) using NF449 provoked a gradual augmentation in I(A) and eliminated the BK-induced effect on I(A,) while the G(i)/(o) antagonist NF023 did not. The application of forskolin or dibutyryl-cAMP mimicked the inhibitory effect of BK on I(A) and abolished the BK-induced effect on I(A). H-89, an inhibitor of PKA, augmented I(A) amplitude and completely eliminated the BK-induced inhibitory effect on I(A). In contrast, activation of PKC by PMA augmented I(A) amplitude. A cAMP assay revealed that BK significantly increased intracellular cAMP level. It is therefore concluded that BK inhibits the I(A) current in Schwann cells by cAMP/PKA-dependent pathways via activation of the B(2) receptor.
authors.affiliation: Institute of Brain Science, School of Life Sciences and State Key Lab of Medical Neurobiology, Fudan University, Shanghai 200433, P.R. China.
authors.forename: Man
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Fei
authors.forename: Yan-Lin
authors.initials: YL
authors.lastname: He
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Yan-Ai
authors.initials: YA
authors.lastname: Mei