POLYAMINE SIGNALING VIA GLIAL CONNEXIN-43 HEMICHANNELS IN RETINA

通过视网膜中的胶质连接蛋白 43 半通道进行多胺信号传导

• 批准号: 8167855
• 负责人: YURIY KUCHERYAVYKH
• 金额: $ 14.53万
• 依托单位: UNIVERSITY OF PUERTO RICO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167855
• 关键词: Cells; Cessation of life; Computer Retrieval of Information on Scientific Projects Database; Connexin 43; Connexins; Data; Enzymes; Funding; Gap Junctions; Glaucoma; Glutamate Receptor; Glutamates; Grant; Institution; Intervention; N-Methyl-D-Aspartate Receptors; Neuroglia; Neurons; Photoreceptors; Physiological; Polyamines; Preparation; Research; Research Personnel; Resources; Retina; Retinal; Signal Transduction; Signaling Molecule; Source; Spermidine; Spermine; Techniques; Testing; Thick; United States National Institutes of Health; Work; excitotoxicity; ganglion cell; insight; kainate; receptor; retinal ischemia; retinal neuron

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The major glial cells in the retina, M¿ller cells, span the whole retinal thickness from photoreceptors to ganglion cells. M¿ller cells contact and even delimit all neuronal compartments and can release neuroactive substances to directly regulate neurons. One likely candidate to regulate retinal neuronal activity is the endogenous polyamine spermine (SPM). The polyamines spermine and spermidine (SPM/SPD) are predominantly located in M¿ller cells in the retina, but modulate many neuronal receptors and channels found on retinal neurons including AMPA, kainate, NMDA receptor channels and Kir channels. Our preliminary data demonstrate release of SPM/SPD from this glia to neuronal network under glial specific treatments. Our working hypothesis is that endogenous SPM acts as a signaling molecule between glial and neuronal cells in the retina: (i) SPM is accumulated and released from M¿ller (glial) cells, potentially through unapposed hemi-gap junctions (hemichannels) and (ii) acts simultaneously on several types of neuronal receptors and channels to modulate retinal neuronal networks. Using electrophysiological and immunocytochemical techniques, we propose to test this hypothesis by the following specific aims: Specific aim 1 To determine if M¿ller glial cells express the biosynthetic enzymes necessary for polyamine synthesis under physiological and pathophysiological conditions. Specific aim 2  To examine SPM flux potentially through connexin hemichannels or P2X7 receptors in retinal M¿ller (glial) cells. Specific aim 3  To determine the effect of spermine on glutamate receptors in isolated retinal neurons and in a retinal whole-mount preparation. The results of these studies will provide insight into spermine-dependent retinal activity and may ultimately result in interventions for glaucoma, retinas ischemia, glutamate excitotoxicity and subsequent neuronal death.

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