Gamma-Aminobutyric Acid Action on Membrane and Electrical Properties of Synaptosomes and Model Lipid Bilayers.

IF 2.3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Membrane Biology Pub Date : 2025-02-09 DOI:10.1007/s00232-025-00339-2

Virjinia Doltchinkova, Victoria Vitkova, Ognyan Petkov, Meglena Kitanova, Angelina Stoyanova-Ivanova, Siya Lozanova, Avgust Ivanov, Chavdar Roumenin

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引用次数: 0

Abstract

Dysfunction of the main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is the underlying reason behind many neurological disorders including Alzheimer's and Huntington's diseases, autism spectrum disorders, anxiety, depression, hypertension, and cardiovascular diseases, among others. Here, we address neurotransmitter-induced alterations of synaptosomal and model membrane electrical properties for elucidating membrane-related biophysical mechanisms of neurological disorders. We focus on membrane surface characteristics of the pinched off nerve endings synaptosomes, which for decades have been a powerful tool in neurobiology. Microelectrophoretic measurements of GABA-treated negatively charged synaptosomes from rat cerebral cortex reveal lower negative zeta potential as a result of reduced electrical charge on the membrane surface at (1-4 h) after isolation. Conversely, enhancement of the surface parameters of synaptosomes (17-22 h) post isolation is obtained due to additional negatively exposed groups on the surface of the vesicles. The electrical properties of bilayer lipid membranes are probed by electrochemical impedance spectroscopy, reporting as light increase of the membrane electrical capacitance in the presence of GABA, likely related to membrane thinning and dielectric permittivity alterations. The neurotransmitter inhibits sodium-potassium as well as the total ATPase activity and slightly enhances magnesium-ATPase of native synaptic membranes. At low (pM) GABA concentrations the activity of acetylcholinesterase (AChE) in synaptic membranes increases. AChE inhibition is reported at higher GABA concentrations. The relation between the surface electrical properties of cells and the enzymatic activity of brain ATPases and AChE, as examined here, are expected to be helpful in the elucidation of membrane-mediated molecular mechanisms relevant to neurological disorders and conditions.

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来源期刊

Journal of Membrane Biology 生物-生化与分子生物学

CiteScore

4.80

自引率

4.20%

发文量

审稿时长

6-12 weeks

期刊介绍： The Journal of Membrane Biology is dedicated to publishing high-quality science related to membrane biology, biochemistry and biophysics. In particular, we welcome work that uses modern experimental or computational methods including but not limited to those with microscopy, diffraction, NMR, computer simulations, or biochemistry aimed at membrane associated or membrane embedded proteins or model membrane systems. These methods might be applied to study topics like membrane protein structure and function, membrane mediated or controlled signaling mechanisms, cell-cell communication via gap junctions, the behavior of proteins and lipids based on monolayer or bilayer systems, or genetic and regulatory mechanisms controlling membrane function. Research articles, short communications and reviews are all welcome. We also encourage authors to consider publishing ''negative'' results where experiments or simulations were well performed, but resulted in unusual or unexpected outcomes without obvious explanations. While we welcome connections to clinical studies, submissions that are primarily clinical in nature or that fail to make connections to the basic science issues of membrane structure, chemistry and function, are not appropriate for the journal. In a similar way, studies that are primarily descriptive and narratives of assays in a clinical or population study are best published in other journals. If you are not certain, it is entirely appropriate to write to us to inquire if your study is a good fit for the journal.