Inhibitory Effectiveness of Gomisin A, a Dibenzocyclooctadiene Lignan Isolated from , on the Amplitude and Gating of Voltage-Gated Na Current.

Gomisin A (Gom A), a lignan isolated from , has been reported produce numerous biological activities. However, its action on the ionic mechanisms remains largely unanswered. The present experiments were undertaken to investigate the possible perturbations of Gom A or other related compounds on different types of membrane ionic currents in electrically excitable cells (i.e., pituitary GH and pancreatic INS-1 cells). The exposure to Gom A led to the differential inhibition of peak and end-pulse components of voltage-gated Na current () in GH cells with effective IC of 6.2 and 0.73 μM, respectively. The steady-state inactivation curve of in the presence of Gom A was shifted towards a more hyperpolarized potential. However, neither changes in the overall current-voltage relationship nor those for the gating charge of the current were demonstrated. The application of neither morin (10 μM) nor hesperidin (10 μM) perturbed the strength of , while sesamine could suppress it. However, in the continued presence of Gom A, the addition of sesamine failed to suppress further. Gom A also effectively suppressed the strength of persistent activated by long ramp voltage command, and further application of tefluthrin effectively attenuated Gom A-mediated inhibition of the current. The presence of Gom A mildly inhibited erg-mediated K current, while a lack of change in the amplitude of hyperpolarization-activated cation current was observed in its presence. Under cell-attached current recordings, the exposure to Gom A resulted in the decreased firing of spontaneous action currents with a minimal change in AC amplitude. In pancreatic INS-1 cells, the presence of Gom A was also noticed to inhibit peak and end-pulse components of differentially with the IC of 5.9 and 0.84 μM, respectively. Taken together, the emerging results presented herein provide the evidence that Gom A can differentially inhibit peak and sustained in endocrine cells (e.g., GH and INS-1 cells).