Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid
Lutein (β,ε-carotene-3,3′-diol), a xanthophyll carotenoid, is found in high concentrations in the macula of the human retina. It has been recognized to exert potential effectiveness in antioxidative and anti-inflammatory properties. However, whether and how its modifications on varying types of plas...
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2022-06-01
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| author | Chao-Wei Chuang Kuo-Pin Chang Hsin-Yen Cho Tzu-Hsien Chuang Meng-Cheng Yu Chao-Liang Wu Sheng-Nan Wu |
| author_facet | Chao-Wei Chuang Kuo-Pin Chang Hsin-Yen Cho Tzu-Hsien Chuang Meng-Cheng Yu Chao-Liang Wu Sheng-Nan Wu |
| author_sort | Chao-Wei Chuang |
| collection | DOAJ |
| description | Lutein (β,ε-carotene-3,3′-diol), a xanthophyll carotenoid, is found in high concentrations in the macula of the human retina. It has been recognized to exert potential effectiveness in antioxidative and anti-inflammatory properties. However, whether and how its modifications on varying types of plasmalemmal ionic currents occur in electrically excitable cells remain incompletely answered. The current hypothesis is that lutein produces any direct adjustments on ionic currents (e.g., hyperpolarization-activated cation current, <i>I</i><sub>h</sub> [or funny current, <i>I</i><sub>f</sub>]). In the present study, GH<sub>3</sub>-cell exposure to lutein resulted in a time-, state- and concentration-dependent reduction in <i>I</i><sub>h</sub> amplitude with an IC<sub>50</sub> value of 4.1 μM. There was a hyperpolarizing shift along the voltage axis in the steady-state activation curve of <i>I</i><sub>h</sub> in the presence of this compound, despite being void of changes in the gating charge of the curve. Under continued exposure to lutein (3 μM), further addition of oxaliplatin (10 μM) or ivabradine (3 μM) could be effective at either reversing or further decreasing lutein-induced suppression of hyperpolarization-evoked <i>I</i><sub>h</sub>, respectively. The voltage-dependent anti-clockwise hysteresis of <i>I</i><sub>h</sub> responding to long-lasting inverted isosceles-triangular ramp concentration-dependently became diminished by adding this compound. However, the addition of 10 μM lutein caused a mild but significant suppression in the amplitude of <i>erg</i>-mediated or A-type K<sup>+</sup> currents. Under current-clamp potential recordings, the sag potential evoked by long-lasting hyperpolarizing current stimulus was reduced under cell exposure to lutein. Altogether, findings from the current observations enabled us to reflect that during cell exposure to lutein used at pharmacologically achievable concentrations, lutein-perturbed inhibition of <i>I</i><sub>h</sub> would be an ionic mechanism underlying its changes in membrane excitability. |
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| language | English |
| last_indexed | 2024-03-09T21:49:45Z |
| publishDate | 2022-06-01 |
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| spelling | doaj.art-53d125111fa04f38a259f0863520b0772023-11-23T20:09:31ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-06-012313718610.3390/ijms23137186Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll CarotenoidChao-Wei Chuang0Kuo-Pin Chang1Hsin-Yen Cho2Tzu-Hsien Chuang3Meng-Cheng Yu4Chao-Liang Wu5Sheng-Nan Wu6Department of Ophthalmology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City 60002, TaiwanDepartment of Ophthalmology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi City 60002, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 70101, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 70101, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 70101, TaiwanDepartment of Medical Research, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi 60002, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 70101, TaiwanLutein (β,ε-carotene-3,3′-diol), a xanthophyll carotenoid, is found in high concentrations in the macula of the human retina. It has been recognized to exert potential effectiveness in antioxidative and anti-inflammatory properties. However, whether and how its modifications on varying types of plasmalemmal ionic currents occur in electrically excitable cells remain incompletely answered. The current hypothesis is that lutein produces any direct adjustments on ionic currents (e.g., hyperpolarization-activated cation current, <i>I</i><sub>h</sub> [or funny current, <i>I</i><sub>f</sub>]). In the present study, GH<sub>3</sub>-cell exposure to lutein resulted in a time-, state- and concentration-dependent reduction in <i>I</i><sub>h</sub> amplitude with an IC<sub>50</sub> value of 4.1 μM. There was a hyperpolarizing shift along the voltage axis in the steady-state activation curve of <i>I</i><sub>h</sub> in the presence of this compound, despite being void of changes in the gating charge of the curve. Under continued exposure to lutein (3 μM), further addition of oxaliplatin (10 μM) or ivabradine (3 μM) could be effective at either reversing or further decreasing lutein-induced suppression of hyperpolarization-evoked <i>I</i><sub>h</sub>, respectively. The voltage-dependent anti-clockwise hysteresis of <i>I</i><sub>h</sub> responding to long-lasting inverted isosceles-triangular ramp concentration-dependently became diminished by adding this compound. However, the addition of 10 μM lutein caused a mild but significant suppression in the amplitude of <i>erg</i>-mediated or A-type K<sup>+</sup> currents. Under current-clamp potential recordings, the sag potential evoked by long-lasting hyperpolarizing current stimulus was reduced under cell exposure to lutein. Altogether, findings from the current observations enabled us to reflect that during cell exposure to lutein used at pharmacologically achievable concentrations, lutein-perturbed inhibition of <i>I</i><sub>h</sub> would be an ionic mechanism underlying its changes in membrane excitability.https://www.mdpi.com/1422-0067/23/13/7186lutein (β,ε-carotene-3,3′-diol or 3,3′-di-hydroxy-β,α-carotene)hyperpolarization-activated cation currentactivation kineticsvoltage-dependent hysteresisK<sup>+</sup> currentsag potential |
| spellingShingle | Chao-Wei Chuang Kuo-Pin Chang Hsin-Yen Cho Tzu-Hsien Chuang Meng-Cheng Yu Chao-Liang Wu Sheng-Nan Wu Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid International Journal of Molecular Sciences lutein (β,ε-carotene-3,3′-diol or 3,3′-di-hydroxy-β,α-carotene) hyperpolarization-activated cation current activation kinetics voltage-dependent hysteresis K<sup>+</sup> current sag potential |
| title | Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid |
| title_full | Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid |
| title_fullStr | Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid |
| title_full_unstemmed | Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid |
| title_short | Characterization of Inhibitory Capability on Hyperpolarization-Activated Cation Current Caused by Lutein (β,ε-Carotene-3,3′-Diol), a Dietary Xanthophyll Carotenoid |
| title_sort | characterization of inhibitory capability on hyperpolarization activated cation current caused by lutein β ε carotene 3 3 diol a dietary xanthophyll carotenoid |
| topic | lutein (β,ε-carotene-3,3′-diol or 3,3′-di-hydroxy-β,α-carotene) hyperpolarization-activated cation current activation kinetics voltage-dependent hysteresis K<sup>+</sup> current sag potential |
| url | https://www.mdpi.com/1422-0067/23/13/7186 |
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