title: Cardiac Slo2.1 Is Required for Volatile Anesthetic Stimulation of K+ Transport and Anesthetic Preconditioning.
abstract: BACKGROUND
  Anesthetic 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.
  
  
  METHODS
  A 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.
  
  
  RESULTS
  In 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.
  
  
  CONCLUSIONS
  Slick (Slo2.1) is required for both VA-stimulated K flux and for the APC-induced cardioprotection.
authors: From the Departments of Anesthesiology (A.P.W., W.R.U., Y.T.W., P.S.B.), Biochemistry (C.O.S.), Pharmacology and Physiology (A.P.W., P.S.B., K.N.), and Medicine (K.N.), University of Rochester Medical Center, Rochester, New York; and Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri (X.-M.X.).
authors: Andrew P
authors: AP
authors: Wojtovich
authors: C Owen
authors: CO
authors: Smith
authors: William R
authors: WR
authors: Urciuoli
authors: Yves T
authors: YT
authors: Wang
authors: Xiao-Ming
authors: XM
authors: Xia
authors: Paul S
authors: PS
authors: Brookes
authors: Keith
authors: K
authors: Nehrke
mesh_terms: D018685:Anesthetics, Inhalation / Q000627:therapeutic use*; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism; D015428:Myocardial Reperfusion Injury / Q000235:genetics* / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D000081033:Potassium Channels, Sodium-Activated; D013793:Thallium / Q000378:metabolism
chemical_list: D018685:Anesthetics, Inhalation; C518649:Kcnt2 protein, mouse; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; D013793:Thallium; D007530:Isoflurane; D011188:Potassium