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Endocannabinoid 2-Arachidonoylglycerol Suppresses LPS-Induced Inhibition of A-Type Potassium Channel Currents in Caudate Nucleus Neurons Through CB1 Receptor

Journal of Molecular Neuroscience volume 59, pages 493–503 (2016)Cite this article

Abstract

Inflammation plays a pivotal role in the pathogenesis of many diseases in the central nervous system. Caudate nucleus (CN), the largest nucleus in the brain, is also implicated in many neurological disorders. 2-Arachidonoylglycerol (2-AG), the most abundant endogenous cannabinoid, has been shown to exhibit neuroprotective effects through its anti-inflammatory action from some proinflammatory stimuli. However, the neuroprotective mechanism of 2-AG is complex and has not been fully understood. A-type K+ channels critically regulate neuronal excitability and have been demonstrated to be associated with some nervous system diseases. The aim of this study was to explore whether A-type K+ channels were involved in neurotoxicity of lipopolysaccharides (LPS) and the neuroprotective mechanism of 2-AG in CN neurons. Whole cell patch clamp recording was used to investigate the influence of LPS on the function of A-type K+ channels and its modulation by 2-AG in primary cultured rat CN neurons. Our findings showed that in cultured CN neurons, LPS significantly decreased the A-type potassium currents (I A) in a voltage-insensitive way. The further data demonstrated that an elevation of 2-AG levels by directly applying exogenous 2-AG or inhibiting monoacylglycerol lipase (MAGL) to prevent 2-AG hydrolysis was capable of suppressing the LPS-induced inhibition of IA and the action of 2-AG is mediated through CB1 receptor-dependant way. The study provides a better understanding of inflammation-related neurological disorders and suggests the therapeutic potential for 2-AG for the treatment of these diseases.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30970930) and China Three Gorges University Foundation for Cultivating Superior Master Degree Dissertation (No. 2015PY056).

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Affiliations

  1. Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei, People’s Republic of China

    Ziliang Zou, Yongli Lu & Hongwei Yang

  2. Third-Grade Pharmacological Laboratory on Chinese Medicine Approved by State Administration of Traditional Chinese Medicine, China Three Gorges University, 443002, Yichang, Hubei, People’s Republic of China

    Yongli Lu & Hongwei Yang

  3. Department of Neurology, The First Hospital of Yichang, Institute of Translational Neuroscience, Three Gorges University College of Medicine, 443000, Yichang, Hubei, People’s Republic of China

    Yunhong Zha

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  1. Ziliang Zou
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  2. Yongli Lu
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  3. Yunhong Zha
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  4. Hongwei Yang
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Correspondence to Hongwei Yang.

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Ziliang Zou and Yongli Lu contributed equally to this work.

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Zou, Z., Lu, Y., Zha, Y. et al. Endocannabinoid 2-Arachidonoylglycerol Suppresses LPS-Induced Inhibition of A-Type Potassium Channel Currents in Caudate Nucleus Neurons Through CB1 Receptor. J Mol Neurosci 59, 493–503 (2016). https://doi.org/10.1007/s12031-016-0761-4

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  • DOI: https://doi.org/10.1007/s12031-016-0761-4

Keywords

  • Caudate nucleus (CN)
  • 2-Arachidonoylglycerol (2-AG)
  • Lipopolysaccharide (LPS)
  • Cannabinoid receptor
  • A-type potassium channel
  • Monoacylglycerol lipase (MAGL)