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

  • Biomedicines. 2023 Sep 27;11(10):2651. doi: 10.3390/biomedicines11102651.
Yen-Chin Liu  1  2  3 ,  Edmund Cheung So  4 ,  Sheng-Nan Wu  5  6  7
Affiliations
  • 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.
PMID: 37893024 DOI: 10.3390/biomedicines11102651
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.

Keywords
M-type K+ current; cannabidiol (CBD); erg-mediated K+ current; hyperpolarization-activated cation current; pituitary cell; voltage-gated Na+ current.
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