Zingerone Modulates Neuronal Voltage-Gated Na + and L-Type Ca 2+ Currents.

Zingerone (ZO), a nontoxic methoxyphenol, has been demonstrated to exert various important biological effects. However, its action on varying types of ionic currents and how they concert in neuronal cells remain incompletely understood. With the aid of patch clamp technology, we investigated the effects of ZO on the amplitude, gating, and hysteresis of plasmalemmal ionic currents from both pituitary tumor (GH 3 ) cells and hippocampal (mHippoE-14) neurons. The exposure of the GH 3 cells to ZO differentially diminished the peak and late components of the I Na . Using a double ramp pulse, the amplitude of the I Na(P) was measured, and the appearance of a hysteresis loop was observed. Moreover, ZO reversed the tefluthrin-mediated augmentation of the hysteretic strength of the I Na(P) and led to a reduction in the I Ca,L . As a double ramp pulse was applied, two types of voltage-dependent hysteresis loops were identified in the I Ca,L , and the replacement with BaCl 2 -attenuated hysteresis of the I Ca,L enhanced the I Ca,L amplitude along with the current amplitude (i.e., the I Ba ). The hysteretic magnitude of the I Ca,L activated by the double pulse was attenuated by ZO. The peak and late I Na in the hippocampal mHippoE-14 neurons was also differentially inhibited by ZO. In addition to acting on the production of reactive oxygen species, ZO produced effects on multiple ionic currents demonstrated herein that, considered together, may significantly impact the functional activities of neuronal cells.