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

By April 29, 2016No Comments
2016 Apr 29. [Epub ahead of print]
Zou Z1, Lu Y1,2, Zha Y3, Yang H4,5.

Abstract

PM 1aInflammation 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.

KEYWORDS:

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

PMID:

 

27129498

 

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