Modulating the Neocortical Extracellular Potassium Concentration In Vivo: Roles for Astrocytes and Energy
Bibliographic record
Abstract
A normally functioning nervous system, neuronal and glial activity are dependent on normal extracellular potassium ion concentration ([K]o). Raised [K]o is associated with several disorders including cortical spreading depression, migraine, stroke, neurotrauma and epilepsy. To avoid neuronal adverse conditions, several processes, including those of an astrocytic nature, and ATP-dependent pumps and channels are involved in regulating the [K]o. This dissertation explores the role of astrocytic gap junctional coupling, astrocytic membrane potential and intracellular ATP concentration ([ATP]i) in the neocortical [K]o regulation/distribution using in vivo electrophysiological techniques combined with optogenetics and pharmacological interventions. Application of gap junctional blockers, carbenoxolone and Gap27, partially modulated the amplitude and shape of the evoked potassium ion (K) response but most noticeably decreased the velocity of the spreading evoked K and spreading depolarization (SD)-like responses. Opening of gap junctions by trimethylamine, slightly decreased the amplitude of the evoked K response and markedly increased the velocity of the redistribution of the evoked K and SD-like events. Photostimulation of eNpHR expressing astrocytes, which hyperpolarizes these cells, resulted in a significantly decreased resting [K]o and evoked K responses, and the amplitude of concomitant SD-like events also decreased. Reducing the [ATP]i using 2,4-dinitrophenol, 2-deoxyglucose or endothelin-1 application led to raised [K]o and SD-like events. It is proposed that the increased [K]o is due to impairment of the Na/K ATPase pump and ATP-sensitive potassium channels in the absence of sufficient ATP because, Na/K ATPase inhibition by ouabain led to increased [K]o and ATP-sensitive potassium channel impairment by glibenclamide resulted in decreased [K]o. In brief, observations presented in this dissertation, suggest that [K]o regulation is only partially modulated by astrocytic gap junction coupling with the most critical impact on the velocity, and not the amplitude of the evoked K and SD-like responses. Also, astrocytic membrane hyperpolarization leads to decreased [K]o. Moreover, a decreased [ATP]i leads to increased [K]o. This dissertation has investigated some of the key mechanisms involved in [K]o dynamics and suggests that modulation of astrocytic membrane potential, astrocytic gap junction coupling, and [ATP]i could be potential tools for altering the cerebral cortical [K]o.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".