Potassium channels as molecular targets of endocannabinoids

Lin, Yu-Fung

doi:10.1080/19336950.2021.1910461

Cited by 17 publications

(7 citation statements)

References 110 publications

(250 reference statements)

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“…Furthermore, K ATP expressed in Xenopus oocytes were inhibited by AEA (CBR independent) with an IC 50 of 8.1 µM (Oz et al, 2007), but activated in rat ventricular myoctyes in a CB2 dependent manner (Li et al, 2012). Notably, the EC 50 ’s of the endocannabinoids studied here on Kir2.1 and Kir4.1 are in a similar range of IC 50 /EC 50 ’s identified for a variety of other channels (Lin, 2021), and thus physiologically relevant.…”

Section: Discussionsupporting

confidence: 60%

Endocannabinoid regulation of inward rectifier potassium (Kir) channels

Mayar,

Borbuliak,

Zoumpoulakis

et al. 2024

Preprint

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The inward rectifier potassium channel Kir2.1 (KCNJ2) is an important regulator of resting membrane potential in both excitable and non-excitable cells. The functions of Kir2.1 channels are dependent on their lipid environment, including the availability of PI(4,5)P2, secondary anionic lipids, cholesterol and long-chain fatty acids acyl coenzyme A (LC-CoA). Endocannabinoids are a class of lipids that are naturally expressed in a variety of cells, including cardiac, neuronal, and immune cells. While these lipids are identified as ligands for cannabinoid receptors (CBRs), there is a growing body of evidence that they can directly regulate the function of numerous ion channels independently of CBRs. Here we examine the effects of a panel of endocannabinoids on Kir2.1 function and demonstrate that a subset of endocannabinoids can alter Kir2.1 conductance to varying degrees independently of CBRs. Using computational and SPR analysis, endocannabinoid regulation of Kir2.1 channels appears to be the result of altered membrane properties, rather than through direct protein-lipid interactions. Furthermore, differences in endocannabinoid effects on Kir4.1 and Kir7.1 channels, indicating that endocannabinoid regulation is not conserved among Kir family members. These findings may have broader implications on the function of cardiac, neuronal and/or immune cells.

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Section: Discussionsupporting

confidence: 60%

Endocannabinoid regulation of inward rectifier potassium (Kir) channels

Mayar,

Borbuliak,

Zoumpoulakis

et al. 2024

Preprint

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“…Endocannabinoids activating TRPV1 have been included in the endovanilloid system [337][338][339]. Recent studies suggest that potassium channels are also the targets of endocannabinoids [340].…”

Section: Endogenous Receptors For Aea and 2-agmentioning

confidence: 99%

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Sionov

Steinberg

2022

Biomedicines

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Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is an urgent need for new treatment protocols that can also target biofilm-embedded bacteria. Many secondary metabolites of plants possess anti-bacterial activities, and especially the phytocannabinoids of the Cannabis sativa L. varieties have reached a renaissance and attracted much attention for their anti-microbial and anti-biofilm activities at concentrations below the cytotoxic threshold on normal mammalian cells. Accordingly, many synthetic cannabinoids have been designed with the intention to increase the specificity and selectivity of the compounds. The structurally unrelated endocannabinoids have also been found to have anti-microbial and anti-biofilm activities. Recent data suggest for a mutual communication between the endocannabinoid system and the gut microbiota. The present review focuses on the anti-microbial activities of phytocannabinoids and endocannabinoids integrated with some selected issues of their many physiological and pharmacological activities.

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“…A potential mechanism might be the inhibition of Na + channels by AM251, which reduces neuronal excitability through blockade of voltage-sensitive Na + channels in the brain [ 35 ]. Another non mutually exclusive possibility is that effects could be due to (endo)-cannabinoid-mediated modulation of BK channels as it has been reported that (endo)-cannabinoids directly interact with and can modify BK channel activity [ 36 ]. As a result, AM251’s effects on modulating excitability changes seen in the 3-AP Purkinje cells could be via modulation of BK function.…”

Section: Discussionmentioning

confidence: 99%

Pharmacologic antagonism of CB1 receptors improves electrophysiological alterations in Purkinje cells exposed to 3-AP

et al. 2023

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Introduction Although ataxia is associated with cerebellar dysfunction, little is known about the effects of 3-AP exposure on Purkinje cell electrophysiological properties. Here, we evaluated these parameters in cerebellar vermis brain slices. Methods Purkinje cells were exposed to artificial cerebrospinal fluid (aCSF) (control) or to 1 mM 3-acetylpyridine (3-AP) in the recording chamber. The effects of a cannabinoid agonist (WIN; 7.5 nmol) and a cannabinoid antagonist (AM; 20 nmol) were evaluated under both conditions. Results Exposure to 3-AP induced dramatic changes in cellular excitability that likely would affect Purkinje cell output. In whole-cell current clamp recordings, 3-AP-exposed Purkinje cells demonstrated a significantly higher frequency of action potentials, a larger afterhyperpolarization (AHP), and a larger rebound of action potentials. In addition, 3-AP caused a significant decrease in the interspike interval (ISI), half-width, and first spike latency. Remarkably, the action potential frequency, AHP amplitude, rebound, ISI, action potential halfwidth, and first spike latency were no longer different from controls in 3-AP cells treated with AM. Sag percentage, on the other hand, showed no significant difference under any treatment condition, indicating that cannabinoids' actions on 3-AP-mediated Purkinje cell changes may not include effects on neuronal excitability through changes of Ih. Conclusions These data show that cannabinoid antagonists reduce the excitability of Purkinje cells following exposure to 3-AP and suggest their potential as therapeutics in cerebellar dysfunctions.

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Potassium channels as molecular targets of endocannabinoids

Cited by 17 publications

References 110 publications

Endocannabinoid regulation of inward rectifier potassium (Kir) channels

Endocannabinoid regulation of inward rectifier potassium (Kir) channels

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Pharmacologic antagonism of CB1 receptors improves electrophysiological alterations in Purkinje cells exposed to 3-AP

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