Evidence for Potentiation of M-Type Potassium Current by Flavonoid Corylin (3-(2,2-Dimethylchromen-6-yl)-7-hydroxychromen-4-one)

Background: Corylin (3-(2,2-dimethylchromen-6-yl)-7-hydroxychromen-4-one), a bioactive flavonoid, has been reported to exercise anti-inflammatory, antineoplastic, and antioxidant effects, and may also possess lifespan-extending properties. Objectives: Any modifications of transmembrane ionic currents produced by corylin remain largely unknown. Methods: The patch-clamp technique and docking prediction were used in this study. Results: In pituitary GH3 somatolactotrophs, corylin concentration-dependently increased the magnitude of the M-type K+ current (IK(M)), with an EC50 of 3.8 μM. Concurrently, the activation time constant of IK(M) was shortened. The addition of linopirdine (10 μM), an IK(M) inhibitor, suppressed the current amplitude. Corylin also induced a leftward shift in the steady-state activation curve and enhanced IK(M) during pulse-train stimulation. Moreover, corylin increases the hysteretic strength of IK(M) evoked by a long-lasting triangular ramp pulse; this effect was attenuated by linopirdine. The stimulatory effect of corylin on IK(M) was not altered by carvedilol or iberiotoxin but was reduced by dapagliflozin. In contrast, depolarization-activated IK(M) was not affected by 17β-estradiol alone. In cell-attached recordings, corylin increased M-type K+ (KM)-channel activity with minimal change in single-channel amplitude, while prolonging the mean open time. This stimulatory effect was reversed by linopirdine or dapagliflozin. Additionally, corylin slightly inhibited the erg-mediated current. Docking analysis further suggested that corylin potentially interacts with residues in KCNQ2 or KCNH2 channels via hydrogen bonding and hydrophobic interactions. Conclusions: These findings suggest that corylin modulates ionic currents, primarily through KM (KCNQ/KV7) channels, which may underlie its in vivo actions and those of related flavonoids. These effects may contribute to the regulation of functional activities of neuronal, neuroendocrine, and endocrine cells.