Cannabidiol Modulates M-Type K+ and Hyperpolarization-Activated Cation Currents

Author:

Liu Yen-Chin123ORCID,So Edmund Cheung4ORCID,Wu Sheng-Nan567ORCID

Affiliation:

1. Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung 80756, Taiwan

2. Department of Anesthesiology, School of Post-Baccalaureate, College of Medicine, Kaohsiung Medical University, Kaohsiung 80756, Taiwan

3. Department of Anesthesiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701401, Taiwan

4. Department of Anesthesia, An-Nan Hospital, China Medical University, Tainan 70965, Taiwan

5. Department of Physiology, National Cheng Kung University Medical College, Tainan 70101, Taiwan

6. School of Medicine, National Sun-Yat Sen University College of Medicine, Kaohsiung 80424, Taiwan

7. Department of Research and Education, An-Nan Hospital, China Medical University, Tainan 70965, Taiwan

Abstract

Cannabidiol (CBD) is a naturally occurring compound found in the Cannabis 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 GH3 cells. Results showed that exposure to CBD led to a concentration-dependent decrease in M-type K+ currents (IK(M)), with an IC50 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 IK(M) was not reversed by naloxone, suggesting that it was not mediated by opioid receptors. The IK(M) elicited by pulse-train stimulation was also decreased upon exposure to CBD. The magnitude of erg-mediated K+ currents was slightly reduced by adding CBD (10 μM), while the density of voltage-gated Na+ currents elicited by a short depolarizing pulse was not affected by it. Additionally, CBD decreased the magnitude of hyperpolarization-activated cation currents (Ih) with an IC50 of 3.3 μM, and the decrease was reversed by oxaliplatin. The quasi-steady-state activation curve of Ih 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 Ih 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.

Funder

Nation Science and Technology Council

An Nan Hospital, Taiwan

Publisher

MDPI AG

Subject

General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)

Reference40 articles.

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