Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents
Cannabidiol (CBD) is a naturally occurring compound found in the <i>Cannabis</i> plant that is known for its potential therapeutic effects. However, its impact on membrane ionic currents remains a topic of debate. This study aimed to investigate how CBD modifies various types of ionic cu...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/11/10/2651 |
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| author | Yen-Chin Liu Edmund Cheung So Sheng-Nan Wu |
| author_facet | Yen-Chin Liu Edmund Cheung So Sheng-Nan Wu |
| author_sort | Yen-Chin Liu |
| collection | DOAJ |
| description | Cannabidiol (CBD) is a naturally occurring compound found in the <i>Cannabis</i> plant that is known for its potential therapeutic effects. However, its impact on membrane ionic currents remains a topic of debate. This study aimed to investigate how CBD modifies various types of ionic currents in pituitary GH<sub>3</sub> cells. Results showed that exposure to CBD led to a concentration-dependent decrease in M-type K<sup>+</sup> currents (<i>I</i><sub>K(M)</sub>), with an IC<sub>50</sub> of 3.6 μM, and caused the quasi-steady-state activation curve of the current to shift to a more depolarized potential with no changes in the curve’s steepness. The CBD-mediated block of <i>I</i><sub>K(M)</sub> was not reversed by naloxone, suggesting that it was not mediated by opioid receptors. The <i>I</i><sub>K(M)</sub> elicited by pulse-train stimulation was also decreased upon exposure to CBD. The magnitude of <i>erg</i>-mediated K<sup>+</sup> currents was slightly reduced by adding CBD (10 μM), while the density of voltage-gated Na<sup>+</sup> currents elicited by a short depolarizing pulse was not affected by it. Additionally, CBD decreased the magnitude of hyperpolarization-activated cation currents (<i>I</i><sub>h</sub>) with an IC<sub>50</sub> of 3.3 μM, and the decrease was reversed by oxaliplatin. The quasi-steady-state activation curve of <i>I</i><sub>h</sub> was shifted in the leftward direction with no changes in the slope factor of the curve. CBD also diminished the strength of voltage-dependent hysteresis on <i>I</i><sub>h</sub> elicited by upright isosceles-triangular ramp voltage. Collectively, these findings suggest that CBD’s modification of ionic currents presented herein is independent of cannabinoid or opioid receptors and may exert a significant impact on the functional activities of excitable cells occurring in vitro or in vivo. |
| first_indexed | 2024-03-10T21:25:27Z |
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| language | English |
| last_indexed | 2024-03-10T21:25:27Z |
| publishDate | 2023-09-01 |
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| spelling | doaj.art-694d440352744b70a75c91ae1b05bd5b2023-11-19T15:45:07ZengMDPI AGBiomedicines2227-90592023-09-011110265110.3390/biomedicines11102651Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation CurrentsYen-Chin Liu0Edmund Cheung So1Sheng-Nan Wu2Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung 80756, TaiwanDepartment of Anesthesia, An-Nan Hospital, China Medical University, Tainan 70965, TaiwanDepartment of Physiology, National Cheng Kung University Medical College, Tainan 70101, TaiwanCannabidiol (CBD) is a naturally occurring compound found in the <i>Cannabis</i> plant that is known for its potential therapeutic effects. However, its impact on membrane ionic currents remains a topic of debate. This study aimed to investigate how CBD modifies various types of ionic currents in pituitary GH<sub>3</sub> cells. Results showed that exposure to CBD led to a concentration-dependent decrease in M-type K<sup>+</sup> currents (<i>I</i><sub>K(M)</sub>), with an IC<sub>50</sub> of 3.6 μM, and caused the quasi-steady-state activation curve of the current to shift to a more depolarized potential with no changes in the curve’s steepness. The CBD-mediated block of <i>I</i><sub>K(M)</sub> was not reversed by naloxone, suggesting that it was not mediated by opioid receptors. The <i>I</i><sub>K(M)</sub> elicited by pulse-train stimulation was also decreased upon exposure to CBD. The magnitude of <i>erg</i>-mediated K<sup>+</sup> currents was slightly reduced by adding CBD (10 μM), while the density of voltage-gated Na<sup>+</sup> currents elicited by a short depolarizing pulse was not affected by it. Additionally, CBD decreased the magnitude of hyperpolarization-activated cation currents (<i>I</i><sub>h</sub>) with an IC<sub>50</sub> of 3.3 μM, and the decrease was reversed by oxaliplatin. The quasi-steady-state activation curve of <i>I</i><sub>h</sub> was shifted in the leftward direction with no changes in the slope factor of the curve. CBD also diminished the strength of voltage-dependent hysteresis on <i>I</i><sub>h</sub> elicited by upright isosceles-triangular ramp voltage. Collectively, these findings suggest that CBD’s modification of ionic currents presented herein is independent of cannabinoid or opioid receptors and may exert a significant impact on the functional activities of excitable cells occurring in vitro or in vivo.https://www.mdpi.com/2227-9059/11/10/2651cannabidiol (CBD)M-type K<sup>+</sup> currenthyperpolarization-activated cation current<i>erg</i>-mediated K<sup>+</sup> currentvoltage-gated Na<sup>+</sup> currentpituitary cell |
| spellingShingle | Yen-Chin Liu Edmund Cheung So Sheng-Nan Wu Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents Biomedicines cannabidiol (CBD) M-type K<sup>+</sup> current hyperpolarization-activated cation current <i>erg</i>-mediated K<sup>+</sup> current voltage-gated Na<sup>+</sup> current pituitary cell |
| title | Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents |
| title_full | Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents |
| title_fullStr | Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents |
| title_full_unstemmed | Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents |
| title_short | Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents |
| title_sort | cannabidiol modulates m type k sup sup and hyperpolarization activated cation currents |
| topic | cannabidiol (CBD) M-type K<sup>+</sup> current hyperpolarization-activated cation current <i>erg</i>-mediated K<sup>+</sup> current voltage-gated Na<sup>+</sup> current pituitary cell |
| url | https://www.mdpi.com/2227-9059/11/10/2651 |
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