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Characterization of Effectiveness in Concerted <i>I</i><sub>h</sub> Inhibition and <i>I</i><sub>K(Ca)</sub> Stimulation by Pterostilbene (Trans-3,5-dimethoxy-4′-hydroxystilbene), a Stilbenoid
oleh: Edmund Cheung So, Zi-Han Gao, Shun Yao Ko, Sheng-Nan Wu
Format: | Article |
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Diterbitkan: | MDPI AG 2020-01-01 |
Deskripsi
Pterostilbene (PTER), a natural dimethylated analog of resveratrol, has been demonstrated to produce anti-neoplastic or neuroprotective actions. However, how and whether this compound can entail any perturbations on ionic currents in electrically excitable cells remains unknown. In whole-cell current recordings, addition of PTER decreased the amplitude of macroscopic <i>I</i><sub>h</sub> during long-lasting hyperpolarization in GH<sub>3</sub> cells in a concentration-dependent manner, with an effective IC<sub>50</sub> value of 0.84 μM. Its presence also shifted the activation curve of <i>I</i><sub>h</sub> along the voltage axis to a more hyperpolarized potential, by 11 mV. PTER at a concentration greater than 10 μM could also suppress <span style="font-variant: small-caps;">l</span>-type Ca<sup>2+</sup> and transient outward K<sup>+</sup> currents in GH<sub>3</sub> cells. With the addition of PTER, <i>I</i><sub>K(Ca)</sub> amplitude was increased, with an EC<sub>50</sub> value of 2.23 μM. This increase in <i>I</i><sub>K(Ca)</sub> amplitude was attenuated by further addition of verruculogen, but not by tolbutamide or TRAM-39. Neither atropine nor nicotine, in the continued presence of PTER, modified the PTER-stimulated <i>I</i><sub>K(Ca)</sub>. PTER (10 μM) slightly suppressed the amplitude of <span style="font-variant: small-caps;">l</span>-type Ca<sup>2+</sup> current and transient outward K<sup>+</sup> current. The presence of PTER (3 μM) was also effective at increasing the open-state probability of large-conductance Ca<sup>2+</sup>-activated K<sup>+</sup> (BK<sub>Ca</sub>) channels identified in hippocampal mHippoE-14 neurons; however, its inability to alter single-channel conductance was detected. Our study highlights evidence to show that PTER has the propensity to perturb ionic currents (e.g., <i>I</i><sub>h</sub> and <i>I</i><sub>K(Ca)</sub>), thereby influencing the functional activities of neurons, and neuroendocrine or endocrine cells.