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Glial KCNQ channels.

胶质 KCNQ 通道。

基本信息

批准号：
10436561
负责人：
Laura Bianchi
金额：
$ 38.38万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-15 至 2027-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10436561
关键词：
Affect Afferent Neurons Alzheimer&apos s Disease Animal Model Astrocytes Behavioral Behavioral Assay Bipolar Disorder Caenorhabditis elegans Cells Complex Consumption Data Electrophysiology (science)Encapsulated Epilepsy Familial benign neonatal epilepsy Family Functional Imaging Genes Goals Heart Homologous Gene Human Huntington Disease Image Individual Knock-out Light Link Mammals Membrane Potentials Mutate Mutation Neonatal Nervous System Physiology Nervous system structure Neuroglia Neurologic Neurons Octanols Odors Organ Output Parkinson Disease Pathogenicity Pathology Pharmacology Phenotype Phosphatidylinositol 4,5-Diphosphate Physiological Potassium Channel Property Regulation Rest Role Sensory Structure Testing Time Voltage-Gated Potassium Channel Work autism spectrum disorder cell type epileptic encephalopathies experimental study gain of function gamma-Aminobutyric Acid genetic approach genetic manipulation in vivo knock-down loss of function mutation member mutant neuronal excitability neuropsychiatry response transcriptome sequencing

项目摘要

Project Summary/Abstract KCNQ channels are members of a conserved family of voltage-gated potassium channels. KCNQ2 through KCNQ5 subunits are expressed in the nervous system, where they regulate neuronal excitability. Epilepsy, autism, and other neurological conditions have been associated with mutations in the KCNQ channel genes expressed in the nervous system. Although evidence supports the expression of KCNQ channels both in neurons and in glia, the role of these channels in glial cells is still unknown. In this study, we use C. elegans to investigate the physiological function of KCNQ channels in glia and the consequences of glial KCNQ pathogenic mutations. Using RNA sequencing we have found that the amphid glia, a pair of glial cells that encapsulate sensory neurons in the amphid sensory organ, express KCNQ worm homolog kqt- 2. Preliminary behavioral and Ca2+ imaging experiments suggest reduced GABA release from glia of kqt-2 knockout and glial knock down worms. Importantly, expression in amphid glia of human KCNQ2 and KCNQ3 genes rescue the kqt-2 knockout phenotype, supporting conservation of function across species. Thus, our preliminary results suggest that glial KCNQ channels may be needed in glia to dampen neuronal activity via GABA release. In this application we will test this hypothesis through the following 3 specific aims: 1) To establish to what extent the function of glia and neurons is altered in kqt-2 knockout; 2) To determine the physiological properties of KCNQ channels in glia; and 3) To establish the consequences of glial KCNQ pathogenic mutations on glial and neuronal structure and function. Our findings suggest a paradigm shift: neuronal output is regulated not only by neuronal KCNQ channels but also by glial KCNQs. Our work will shed light on the underlying mechanism of this regulation and will determine the contribution of pathogenic glial KCNQ mutation to the expression of the phenotype.

项目总结/文摘