Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning
| Autor: | C. Owen Smith, Paul S. Brookes, Yves T. Wang, Andrew P. Wojtovich, Keith Nehrke, Xiao Ming Xia, William R. Urciuoli |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Potassium Channels Biological Transport Active Stimulation Myocardial Reperfusion Injury Potassium Channels Sodium-Activated Mitochondria Heart Article 03 medical and health sciences Mice Internal medicine medicine Animals Humans Myocytes Cardiac Thallium K channels Cardioprotection Mice Knockout Isoflurane business.industry Volatile anesthetic Infarct size Potassium channel Mice Inbred C57BL 030104 developmental biology Anesthesiology and Pain Medicine Endocrinology HEK293 Cells Anesthetic Anesthetics Inhalation Ischemic Preconditioning Myocardial Cardiology Potassium business medicine.drug |
| Zdroj: | Anesthesiology. 124(5) |
| ISSN: | 1528-1175 |
| Popis: | BackgroundAnesthetic preconditioning (APC) is a clinically important phenomenon in which volatile anesthetics (VAs) protect tissues such as heart against ischemic injury. The mechanism of APC is thought to involve K+ channels encoded by the Slo gene family, and the authors showed previously that slo-2 is required for APC in Caenorhabditis elegans. Thus, the authors hypothesized that a slo-2 ortholog may mediate APC-induced cardioprotection in mammals.MethodsA perfused heart model of ischemia–reperfusion injury, a fluorescent assay for K+ flux, and mice lacking Slo2.1 (Slick), Slo2.2 (Slack), or both (double knockouts, Slo2.x dKO) were used to test whether these channels are required for APC-induced cardioprotection and for cardiomyocyte or mitochondrial K+ transport.ResultsIn wild-type (WT) hearts, APC improved post-ischemia–reperfusion functional recovery (APC = 39.5 ± 3.7% of preischemic rate × pressure product vs. 20.3 ± 2.3% in controls, means ± SEM, P = 0.00051, unpaired two-tailed t test, n = 8) and lowered infarct size (APC = 29.0 ± 4.8% of LV area vs. 51.4 ± 4.5% in controls, P = 0.0043, n = 8). Protection by APC was absent in hearts from Slo2.1−/− mice (% recovery APC = 14.6 ± 2.6% vs. 16.5 ± 2.1% in controls, P = 0.569, n = 8 to 9, infarct APC = 52.2 ± 5.4% vs. 53.5 ± 4.7% in controls, P = 0.865, n = 8 to 9). APC protection was also absent in Slo2.x dKO hearts (% recovery APC = 11.0 ± 1.7% vs. 11.9 ± 2.2% in controls, P = 0.725, n = 8, infarct APC = 51.6 ± 4.4% vs. 50.5 ± 3.9% in controls, P = 0.855, n = 8). Meanwhile, Slo2.2−/− hearts responded similar to WT (% recovery APC = 41.9 ± 4.0% vs. 18.0 ± 2.5% in controls, P = 0.00016, n = 8, infarct APC = 25.2 ± 1.3% vs. 50.8 ± 3.3% in controls, P < 0.000005, n = 8). Furthermore, VA-stimulated K+ transport seen in cardiomyocytes or mitochondria from WT or Slo2.2−/− mice was absent in Slo2.1−/− or Slo2.x dKO.ConclusionSlick (Slo2.1) is required for both VA-stimulated K+ flux and for the APC-induced cardioprotection. |
| Databáze: | OpenAIRE |
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