Author response: Cannabidiol interactions with voltage-gated sodium channels

Sait, Lily Goodyer; Sula, Altin; Ghovanloo, Mohammad‐Reza; Hollingworth, David; Ruben, Peter C.; Wallace, B.A.

doi:10.7554/elife.58593.sa2

Cited by 1 publication

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Since cannabinoids are lipids that are embedded in the lipid bilayer, they can alter channel function by altering membrane properties and/or directly binding the channel. Both mechanisms appear to be important for the regulation of Nav's by CBD (Ghovanloo et al, 2018 , 2021 ; Sait et al, 2020 ) while TRPV2 directly binds CBD in the transmembrane helices (Pumroy et al, 2019 ). Changes to membrane fluidity were induced by the treatment of cells by TX-100, a non-ionic surfactant that has been shown to increase membrane fluidity (Ingolfsson et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

“…Direct activation of chloride ion channels (α 1 and α 2 β glycine receptors) by CBD has been reported with an EC 50 of 132.4 and 144.3 μM (Ahrens et al, 2009 ). Sodium channel, NavMs, and α 7 -nicotinic acethylcholine (α 7 nACh) are inhibited by CBD with an IC 50 of 17.8 (Sait et al, 2020 ) and 11.3 μM (Mahgoub et al, 2013 ), respectively. Kv1.2 channels are inhibited by THC with an IC 50 of 2.4 μM (Poling et al, 1996 ), while human ether-à-go-go (hERG) channels are inhibited with an IC 50 of 10.3 μM (Orvos et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Direct Regulation of Hyperpolarization-Activated Cyclic-Nucleotide Gated (HCN1) Channels by Cannabinoids

Mayar

Memarpoor-Yazdi

Makky

et al. 2022

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Cannabinoids are a broad class of molecules that act primarily on neurons, affecting pain sensation, appetite, mood, learning, and memory. In addition to interacting with specific cannabinoid receptors (CBRs), cannabinoids can directly modulate the function of various ion channels. Here, we examine whether cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), the most prevalent phytocannabinoids in Cannabis sativa, can regulate the function of hyperpolarization-activated cyclic-nucleotide-gated (HCN1) channels independently of CBRs. HCN1 channels were expressed in Xenopus oocytes since they do not express CBRs, and the effects of cannabinoid treatment on HCN1 currents were examined by a two-electrode voltage clamp. We observe opposing effects of CBD and THC on HCN1 current, with CBD acting to stimulate HCN1 function, while THC inhibited current. These effects persist in HCN1 channels lacking the cyclic-nucleotide binding domain (HCN1ΔCNBD). However, changes to membrane fluidity, examined by treating cells with TX-100, inhibited HCN1 current had more pronounced effects on the voltage-dependence and kinetics of activation than THC, suggesting this is not the primary mechanism of HCN1 regulation by cannabinoids. Our findings may contribute to the overall understanding of how cannabinoids may act as promising therapeutic molecules for the treatment of several neurological disorders in which HCN function is disturbed.

show abstract