Cannabidiol Modulates M-Type K<sup>+</sup> and Hyperpolarization-Activated Cation Currents

oleh: Yen-Chin Liu, Edmund Cheung So, Sheng-Nan Wu

Format: Article
Diterbitkan: MDPI AG 2023-09-01

Deskripsi

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.