Inhibitory Effectiveness of Gomisin A, a Dibenzocyclooctadiene Lignan Isolated from Schizandra chinensis, on the Amplitude and Gating of Voltage-Gated Na(+) Current

Gomisin A (Gom A), a lignan isolated from Schisandra chinensis, 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(3) 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 (I(Na)) in GH(3) cells with effective IC(50) of 6.2 and 0.73 μM, respectively. The steady-state inactivation curve of I(Na) 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 I(Na), while sesamine could suppress it. However, in the continued presence of Gom A, the addition of sesamine failed to suppress I(Na) further. Gom A also effectively suppressed the strength of persistent I(Na) 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 I(Na) differentially with the IC(50) 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 I(Na) in endocrine cells (e.g., GH(3) and INS-1 cells).