Abstract
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 Ih during long-lasting hyperpolarization in GH3 cells in a concentration-dependent manner, with an effective IC50 value of 0.84 μM. Its presence also shifted the activation curve of Ih along the voltage axis to a more hyperpolarized potential, by 11 mV. PTER at a concentration greater than 10 μM could also suppress l-type Ca2+ and transient outward K+ currents in GH3 cells. With the addition of PTER, IK(Ca) amplitude was increased, with an EC50 value of 2.23 μM. This increase in IK(Ca) 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 IK(Ca). PTER (10 μM) slightly suppressed the amplitude of l-type Ca2+ current and transient outward K+ current. The presence of PTER (3 μM) was also effective at increasing the open-state probability of large-conductance Ca2+-activated K+ (BKCa) 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., Ih and IK(Ca)), thereby influencing the functional activities of neurons, and neuroendocrine or endocrine cells.
Highlights
Pterostilbene (PTER, trans-3,5-dimethoxy-4 -hydroxystilbene) is a natural dimethylated analog of resveratrol and was named after a natural phenolic compound found in Pterocarpus marsupium Roxb. (Fabaceae), which is native to India, Nepal, and Sri Lanka, and is one of the active compounds in the extracts of P. marsupium that were used in Ayurvedic medicine for the treatment of various disorders [1]
Within 1 min of exposing cells to different concentrations of PTER, the amplitude of Ih activated during 2-s membrane hyperpolarization to −110 mV from a holding potential of −40 mV was progressively reduced (Figure 1A)
The steady state activation curve of Ih was distinctly shifted to more hyperpolarizing potentials by 11 mV, producing channel opening at more negative voltages
Summary
Pterostilbene (PTER, trans-3,5-dimethoxy-4 -hydroxystilbene) is a natural dimethylated analog of resveratrol and was named after a natural phenolic compound found in Pterocarpus marsupium Roxb. (Fabaceae), which is native to India, Nepal, and Sri Lanka, and is one of the active compounds in the extracts of P. marsupium that were used in Ayurvedic medicine for the treatment of various disorders [1]. (Fabaceae), which is native to India, Nepal, and Sri Lanka, and is one of the active compounds in the extracts of P. marsupium that were used in Ayurvedic medicine for the treatment of various disorders [1] This compound has been reported to have benefits for the prevention or treatment of different kinds of cancers, as mounting evidence has demonstrated its inhibitory effects on almost every cellular event that promotes tumor progression toward metastasis in apoptosis-dependent or apoptosis-independent manners [2,3,4,5,6,7,8,9,10,11,12,13]. Whether this agent is capable of perturbing different types of membrane ionic currents in central neurons is not thoroughly investigated, resveratrol, a phytoalexin, has previously been demonstrated to modify large-conductance Ca2+-activated K+ (BKCa) channels and voltage-gated Na+ currents in various types of cells including vascular endothelial cells, cardiac fibroblasts and cortical neurons [29,30,31]
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