磺酰脲类受体2型依赖的KATP通道在缺血预适应中的调控作用-英文.pptVIP

The Glibenclamide-Sensitive KATP Current is Absent in the Mutant Myocytes and VSM Cells Acknowledgements * Regulation and Roles of the Sulfonylurea Receptor 2-Based KATP Channels in Ischemic Preconditioning Bin Ye1, Jie-lin Pu1, Tomoyki Wada1, Jason Sims2, Stacie Kroboth1, Douglas Stoller1, Elizabeth McNally3, Jonathan Makielski1, Nian-Qing Shi1* nqs@medicine.wisc.edu 1Department of Medicine, University of Wisconsin, Madison, WI USA 2Department of Pharmacology, University of Wisconsin, Madison, WI USA 3Department of Medicine, The University of Chicago, Chicago, IL USA The Cellular and Molecular Arrhythmia Research Program Ion Channels Play Pivotal Roles in Cardiac Functions and Protection ? Situate on plasma membrane ? Contain multiple transmembrane helixes ? Opening of ion channels is within milliseconds ? Impact the electrophysiological state of the cell ? Mutations in ion channels are linked to many cardiovascular diseases (i.e. Long QT syndrome) ? Noma (1983): Sarcolemmal KATP ? Inoue et al. (1991): Mitochondrial KATP K+ Mitochondrion K+ K+ Plasma membrane KATP channels open in ischemia like metabolic sensors of the cell Cardiac ATP-sensitive Potassium Channels (KATP) Reviewed by Shi, Ye, Makielski (2005) JMCC 39:51 N 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 C Walker A Walker B Sulfonylurea Receptor (ATP-binding cassette protein) SUR2A (Major cardiac splice variant) SUR2B (Major smooth muscle splice variant) 175 kDa RKR M1 M2 P loop N C RKR Pore (K+ inward rectifier) Kir6.2 48 kDa Structure of Cardiac KATP Channels TMD0 TMD1 TMD2 Ischemia is a disease condition where the heart has insufficient levels of oxygen and blood supply Acute myocardial infarction is a life-threatening event that can cause sudden death and heart failure B