title: Effect of Homocysteine on Voltage-Gated Sodium Channel Currents in Primary Cultured Rat Caudate Nucleus Neurons and Its Modulation by 2-Arachidonylglycerol.
abstract: Homocysteine (Hcy) is an important risk factor for Alzheimer's disease (AD) and other neurodegenerative diseases. 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 from many stimuli in the central nervous system (CNS). Furthermore, it has been reported that voltage-gated sodium channels (VGSCs) are the common targets of many neuronal damages and drugs. However, it is still not clear whether VGSCs are involved in the neurotoxicity of Hcy and the neuroprotective effect of 2-AG in CN neurons. In the present study, whole-cell patch clamp recording was used to invest the action of Hcy on sodium currents in primary cultured rat CN neurons and its modulation by 2-AG. The results showed that in cultured CN neurons, pathological concentration of Hcy (100 μM) significantly increased the voltage-gated sodium currents (I(Na)) and produced a hyperpolarizing shift in the activation-voltage curve of I(Na). The further data demonstrated 2-AG is capable of suppressing elevation of Hcy-induced increase in I(Na) and hyperpolarizing shift of activation curves most partly through CB1 receptor-dependent way. Our study provides a better understanding of Hcy-associated neurological disorders and suggests the therapeutic potential for 2-AG for the treatment of these diseases.
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei,, People's Republic of China.
authors.forename: Ziliang
authors.initials: Z
authors.lastname: Zou
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei,, People's Republic of China.|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.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei,, People's Republic of China.
authors.forename: Manman
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Physiology and Pathophysiology, College of Medical Sciences, China Three Gorges University, 8 University Road, 443002, Yichang, Hubei,, People's Republic of China. yhw0224@yahoo.com.|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. yhw0224@yahoo.com.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Yang
mesh_terms: D000200:Action Potentials; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D063388:Endocannabinoids / Q000494:pharmacology*; D005989:Glycerides / Q000494:pharmacology*; D006710:Homocysteine / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D061566:Voltage-Gated Sodium Channels / Q000378:metabolism*
chemical_list: D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D063388:Endocannabinoids; D005989:Glycerides; D018696:Neuroprotective Agents; D061566:Voltage-Gated Sodium Channels; D006710:Homocysteine; C094503:glyceryl 2-arachidonate
keywords: 2-Arachidonoylglycerol (2-AG); Cannabinoid receptor; Caudate nucleus (CN); Homocysteine (Hcy); Sodium channel; Whole patch clamp