The role of the ATP-sensitive K(+) current as a mechanism of training-induced cardioprotection against ischemia/reperfusion damage

Exercise training increases resistance of the heart to damage and improves cardiac recovery following a heart attack. This 'cardioprotective' effect has been demonstrated in both clinical and experimental settings. However, the cellular basis for the protective effect has yet to be determined. Chronic exercise has been shown to elicit an elevation of heat shock protein (HSP) levels in the heart. The increase in HSP has been associated with cardioprotection against post-ischemic injury. This HSP effect may be mediated via the operation of the ATP-sensitive potassium channels (KATP) on the cell membrane. These channels open when the cellular energy supply (i.e. [ATP]) declines, as it does during ischemia, and they have been implicated in the cardioprotective process. The purpose of these studies was to determine if the KATP channel operation and the current conducted through these channels (IK ATP) are associated with training-induced cardioprotection. To do so, we conducted experiments on whole hearts and single cells isolated from trained (Tr) and sedentary (Sed) rats.; Heart stiffness did not increase significantly following ischemia in the Tr group where it did in the Sed group. Training did not elicit an improvement in myocardial contractile function following ischemia even though HSP content was elevated in Tr hearts. The application of glibenclamide (GLIB), a drug that blocks the KATP channels, improved recovery of hearts from both Tr and Sed animals. Interestingly, hearts from Tr animals responded faster to the drug, suggesting some modification of KATP channel properties due to exercise training.; Our single cell study revealed that, in response to a standardized bout of anoxia, fewer cells from Tr hearts expressed IKATP. Moreover, IKATP was smaller and occurred later in the cells from Tr animals. Collectively, these results suggest that exercise training does influence the KATP channel and/or IKATP properties. We have shown that KATP channel blockade can improve the functional recovery of the heart following a severe bout of ischemia. Exercise training may elicit a similar effect via adaptations that favor channel closure. Similarly, our data indicate that the clinical administration of a KATP channel antagonist at the onset of reperfusion may enhance the functional recovery of patients experiencing an ischemic episode or heart attack.