The role of KATP channels in mitochondrial function and neurite outgrowth: implications in peripheral neuropathy
Bibliographic record
Abstract
Dorsal root ganglion (DRG) sensory neurons play a critical role in processing and modulation of sensory information, including that experienced in peripheral neuropathy. In response to injury of peripheral nerves the DRG undergo changes in potassium channel (K+) function including KATP channels. KATP channels are integral in the regulation of membrane excitability and inhibited by physiological ATP and activated during events of energy depletion, such as metabolic stress. KATP activation plays a neuroprotective role in peripheral neuropathy via membrane hyperpolarization, decreased cell excitability and prevention of cell death. Similarly, the AMP-activated protein kinase (AMPK) signaling pathway enhances mitochondrial functioning and plays a neuroprotective role in peripheral neuropathy. Hypothesis: agonists of KATP channels enhance mitochondrial function and neurite outgrowth via the AMPK pathway and modulate neuronal excitability in DRG neurons. DRG neurons from adult Sprague-Dawley male rats were isolated and cultured under defined conditions. KATP channel openers pinacidil and VU0071063 increased levels of phosphorylated AMPK in a dose and time dependent manner. Additionally, opening of KATP channels augmented neurite outgrowth in the DRG neurons. Interestingly, pinacidil as well as VU0071063 treatment resulted in decreased ATP production as well as coupling efficiency and negatively impacted a plethora of other oxidative phosphorylation parameters. Lastly, pharmacological inhibition of AMPK via Compound C negated the enhancement effect of pinacidil and VU0071063 on neurite outgrowth. This data confirmed the ability of AMPK to act downstream of KATP channels and acts as a key mediator of KATP opening effects on neurite outgrowth. This study reveals for the first time that opening of KATP channels increases AMPK activity and augments neurite outgrowth. However, this mechanism of action of KATP activation did not positively effect mitochondrial respiration. The ability of pharmacological opening of KATP channels to drive neurite outgrowth indicate a potential therapeutic application in peripheral neuropathy.
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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 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".