Role of Ca<sup>2+</sup>-Activated K<sup>+</sup>Channels And Connexin40 In Response To Transient Ischemia In Isolated Rat Hearts
Notice bibliographique
Résumé
Background: Ischemic heart disease (IHD) is a leading cause of death worldwide. Once an ischemic attack occurs, primary myocardial reperfusion remains the gold standard treatment; however, ischemia-reperfusion (IR) injury contributes to myocardial damage and subsequent heart failure. Thus, there is a clinical need to further understand the mechanisms underlying the response of the heart to ischemia that leads to IR injury and to identify novel therapeutic targets. In this study, we have tested two hypotheses in isolated perfused rat heart: 1. Pharmacological activation of cardiac mitochondrial small (SK Ca ) and intermediate conductance (IK Ca ) Ca 2+ -activated K + channels may prevent I/R injury. 2. Loss of Connexin40 (Cx40), which is associated with impaired cardiac electrical coupling, may exacerbate I/R injury. Methods: Male Sprague Dawley rats, and male and female Cx40 knockout rats (Wistar background) were euthanized using sodium pentobarbitol anesthesia followed by decapitation. Hearts were rapidly excised, cannulated via the ascending aorta and perfused in Langendorff mode with warmed Krebs buffer at a constant flow rate. Left ventricular pressure and heart rate were recorded and left ventricular developed pressure (LVDP) was calculated as the difference between left ventricular systolic pressure (LVSP) and LVEDP. Hearts were perfused under normoxic conditions for 30 minutes before global no-flow ischemia was induced by clamping the aortic inflow line and switching off the pump for 15 minutes. The pump was restarted, and the clamp reopened, and the hearts perfused aerobically for a further 45 minutes. Activators of SK Ca and IK Ca channels were added to the perfusate 10 minutes prior to induction of ischemia. Data were analyzed using a two-way ANOVA was performed separately for pre- and post-ischemia. Results: Together, CyPPA and SKA-31 (both 10 microM), activators of SK Ca and IK Ca channels respectively, enhanced recovery following ischemia in isolated Sprague-Dawley rat hearts increasing post-ischemic LVDP from 5.9 +/- 1.7 to 72.6 +/- 2.3 mmHg (p<0.01; n=6). This effect was partially reduced by inhibitors of SK Ca and IK Ca channels but post-ischemic LVDP was still significantly greater than control at 43.9 =/- 3.6 mmHg (p<0.01; n=6). In isolated hearts from both male and female rats lacking Cx40, post-ischemic functional recovery was significantly impaired compared to controls: 1.4 +/- 1.9 and 15.7 +/- 3.4 compared to 24 +/- 1.6 and 34.6 +/- 4.2 mmHg, respectively, (n=5-15). Conclusions: We have shown that small molecule activators of SK Ca and IK Ca channels may protect against IR injury in isolated perfused hearts whereas loss of Cx 40, a protein which mediates cellular electrical coupling, exacerbates IR damage. This study provides new insights into the role of K Ca channels and opens the possibility that they may be therapeutic targets to protect against IR injury in the heart. Heart & Stroke Foundation Canada. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».