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| Content Provider | PubMed Central |
|---|---|
| Author | Suzuki, Masashi Sasaki, Norihito Miki, Takashi Sakamoto, Naoya Yuki, Ohmoto-sekine Tamagawa, Masaji Seino, Susumu Eduardo, Marbán Nakaya, Haruaki |
| Copyright Year | 2002 |
| Abstract | Recently it has been postulated that mitochondrial ATP-sensitive K+ (mitoKATP) channels rather than sarcolemmal KATP (sarcKATP) channels are important as end effectors and/or triggers of ischemic preconditioning (IPC). To define the pathophysiological significance of sarcKATP channels, we conducted functional experiments using Kir6.2-deficient (KO) mice. Metabolic inhibition with glucose-free, dinitrophenol-containing solution activated sarcKATP current and shortened the action potential duration in ventricular cells isolated from wild-type (WT) but not KO mice. MitoKATP channel function was preserved in KO ventricular cells. In anesthetized mice, IPC reduced the infarct size in WT but not KO mice. Following global ischemia/reperfusion, the increase of left ventricular end-diastolic pressure during ischemia was more marked, and the recovery of contractile function was worse, in KO hearts than in WT hearts. Treatment with HMR1098, a sarcKATP channel blocker, but not 5-hydroxydecanoate, a mitoKATP channel blocker, produced a deterioration of contractile function in WT hearts comparable to that of KO hearts. These findings suggest that sarcKATP channels figures prominently in modulating ischemia/reperfusion injury in the mouse. The rapid heart rate of the mouse (>600 beats per minute) may magnify the relative importance of sarcKATP channels during ischemia, prompting caution in the extrapolation of the conclusions to larger mammals. |
| Related Links | http://dx.doi.org/10.1172/jci0214270 |
| Ending Page | 516 |
| Page Count | 8 |
| Starting Page | 509 |
| File Format | |
| ISSN | 00219738 |
| e-ISSN | 15588238 |
| Journal | The Journal of Clinical Investigation |
| Issue Number | 4 |
| Volume Number | 109 |
| Language | English |
| Publisher | American Society for Clinical Investigation |
| Publisher Date | 2002-02-15 |
| Access Restriction | Open |
| Rights Holder | American Society for Clinical Investigation |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine |
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