Hearts lacking plasma membrane K<sub>ATP</sub> channels display changes in basal aerobic metabolic substrate preference and AMPK activity
Bibliographic record
Abstract
Cardiac ATP-sensitive K + (K ATP ) channels couple changes in cellular metabolism to membrane excitability and are activated during metabolic stress, although under basal aerobic conditions, K ATP channels are thought to be predominately closed. Despite intense research into the roles of K ATP channels during metabolic stress, their contribution to aerobic basal cardiac metabolism has not been previously investigated. Hearts from Kir6.2 +/+ and Kir6.2 −/− mice were perfused in working mode, and rates of glycolysis, fatty acid oxidation, and glucose oxidation were measured. Changes in activation/expression of proteins regulating metabolism were probed by Western blot analysis. Despite cardiac mechanical function and metabolic efficiency being similar in both groups, hearts from Kir6.2 −/− mice displayed an approximately twofold increase in fatty acid oxidation and a 0.45-fold reduction in glycolytic rates but similar glucose oxidation rates compared with hearts from Kir6.2 +/+ mice. Kir6.2 −/− hearts also possessed elevated levels of activated AMP-activated protein kinase (AMPK), higher glycogen content, and reduced mitochondrial density. Moreover, activation of AMPK by isoproterenol or diazoxide was significantly blunted in Kir6.2 −/− hearts. These data indicate that K ATP channel ablation alters aerobic basal cardiac metabolism. The observed increase in fatty acid oxidation and decreased glycolysis before any metabolic insult may contribute to the poor recovery observed in Kir6.2 −/− hearts in response to exercise or ischemia-reperfusion injury. Therefore, K ATP channels may play an important role in the regulation of cardiac metabolism through AMPK signaling. NEW & NOTEWORTHY In this study, we show that genetic ablation of plasma membrane ATP-sensitive K + channels results in pronounced changes in cardiac metabolic substrate preference and AMP-activated protein kinase activity. These results suggest that ATP-sensitive K + channels may play a novel role in regulating metabolism in addition to their well-documented effects on ionic homeostasis during periods of stress.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".