Transcriptional profiling of neuronal ion channels in dorsal root ganglion-derived immortal cell line (F-11) under different culture conditions.
Transcriptional profiling of neuronal ion channels in dorsal root ganglion-derived immortal cell line (F-11) under different culture conditions.
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不同培养条件下背根神经节来源的永生细胞系（F-11）神经元离子通道的转录谱。
DOI：
10.1007/s44164-022-00036-7
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Nair,LakshmiS
中科院分区：
文献类型：
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作者：
Morato,ErickOrozco;Knight,Brittany;Nair,LakshmiS
病理性疼痛是一种普遍的疾病，影响大多数患有各种基础疾病的成年人。目前可用的药理学疼痛治疗具有与其长期使用相关的几种负面和潜在危及生命的副作用。由于疼痛感知的异质性和导致疼痛的神经元机制的多样性，高通量筛选可能具有潜在镇痛特性的小分子对于确定既有效又安全的新镇痛治疗是必不可少的。F-11杂交永生化细胞系是目前可用于药物筛选的背根神经节（DRG）细胞系之一。虽然F-11细胞通常被用作初级DRG感觉神经元的类似物，但它们在生理特性上显著不同。本研究探讨了分化方案对F-11细胞中成熟神经元离子通道和受体表达的影响。使用超过80个神经元离子通道和受体（包括电压门控离子通道、瞬时受体电位通道和大麻素受体）的定制基因阵列，我们评估了以下组：对照F-11细胞;在不同培养条件下培养的F-11细胞和小鼠DRG组织。发现F-11细胞中大多数研究的离子通道和受体的表达谱低于原代小鼠DRG神经元。与对照F-11细胞相比，在低血清（LSM）条件下培养的F-11细胞增加了几个研究目标的表达，包括电压门控离子通道和大麻素受体。该研究表明，培养条件显着调制所研究的离子通道和受体的转录表达，并且长期培养（21天）可能会对许多所研究的目标的表达产生不利影响。
Pathological pain is a prevalent condition that affects majority of adults with a variety of underlying disease conditions. Current available pharmacological pain treatments have several negative and potentially life-threatening side effects associated with their long-term use. Due to the heterogeneity of pain perception and the diversity of neuronal mechanisms that contribute to pain, high-throughput screening of small molecules that may have underlying analgesic properties is essential for identifying new analgesic treatments that are both effective and safe. The F-11 hybrid immortalized cell line is one of the currently available dorsal root ganglion (DRG) cell lines used for drug screening. While F-11 cells are commonly used as analogs to primary DRG sensory neurons, they differ significantly in physiological properties. The present study investigated the impact of differentiation protocols on the expression of mature neuron ion channels and receptors in F-11 cells. Using a customized gene array of more than eighty neuronal ion channels and receptors including voltage-gated ion channels, transient receptor potential channels, and cannabinoid receptors, we assessed the following groups: control F-11 cells; F-11 cells cultured under different culture conditions, and murine DRG tissue. The expression profiles of majority of the investigated ion channels and receptors in F-11 cells were found to be lower compared to primary mouse DRG neurons. F-11 cells cultured under low serum (LSM) conditions had increased expression of several investigated targets including voltage-gated ion channels and cannabinoid receptors when compared to control F-11 cells. The study showed that the culture conditions significantly modulated the transcriptional expression of studied ion channels and receptors, and that long-term culture (21 days) may adversely affect the expression of many of the studied targets.