Investigating the effects of impermeant anions on the electrical and computational properties on neurons

Master Thesis

2023

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Impermeant anions (proteins, amino acids, etc.) are negatively charged ions that are unable to traverse the cell membrane. Impermeant anion quantities and their average charge vary with metabolism as well as protein and nucleic acid synthesis/turnover.The effect of spatiotemporal changes to impermeant anions on neurons is poorly understood. Using a multicompartment electrodiffusion-based computational model I investigated the influence of impermeant anions on neuronal cellular physiology, passive cable properties, and synaptic integration. Spatial differences in the average charge of impermeant anions result in a nonisopotential dendrite with ionic microdomains. At steady state local discrepancies in membrane potentials and ion concentrations do not impact the passive or active electrical properties of neurons as ionic driving forces are unchanged, irrespective of impermeant anion mean charge. These findings explain how electrical signalling remains consistent in the face of an ever-changing impermeant anion milieu with implications related to our understanding of both normal and pathological neuronal physiology.
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