title: Cardioprotection afforded by chronic exercise is mediated by the sarcolemmal, and not the mitochondrial, isoform of the KATP channel in the rat.
abstract: This study was conducted to examine the role of myocardial ATP-sensitive potassium (K(ATP)) channels in exercise-induced protection from ischaemia-reperfusion (I-R) injury. Female rats were either sedentary (Sed) or exercised for 12 weeks (Tr). Hearts were excised and underwent a 1-2 h regional I-R protocol. Prior to ischaemia, hearts were subjected to pharmacological blockade of the sarcolemmal K(ATP) channel with HMR 1098 (SedHMR and TrHMR), mitochondrial blockade with 5-hydroxydecanoic acid (5HD; Sed5HD and Tr5HD), or perfused with buffer containing no drug (Sed and Tr). Infarct size was significantly smaller in hearts from Tr animals (35.4 +/- 2.3 versus 44.7 +/- 3.0% of the zone at risk for Tr and Sed, respectively). Mitochondrial K(ATP) blockade did not abolish the training-induced infarct size reduction (30.0 +/- 3.4 versus 38.0 +/- 2.6 in Tr5HD and Sed5HD, respectively); however, sarcolemmal K(ATP) blockade completely eradicated the training-induced cardioprotection. Infarct size was 71.2 +/- 3.3 and 64.0 +/- 2.4% of the zone at risk for TrHMR and Sed HMR. The role of sarcolemmal K(ATP) channels in Tr-induced protection was also supported by significant increases in both subunits of the sarcolemmal K(ATP) channel following training. LV developed pressure was better preserved in hearts from Tr animals, and was not influenced by addition of HMR 1098. 5HD decreased pressure development regardless of training status, from 15 min of ischaemia through the duration of the protocol. This mechanical dysfunction was likely to be due to a 5HD-induced increase in myocardial Ca2+ content following I-R. The major findings of the present study are: (1) unlike all other known forms of delayed cardioprotection, infarct sparing following chronic exercise was not abolished by 5HD; (2) pharmacological blockade of the sarcolemmal K(ATP) channel nullified the cardioprotective benefits of exercise training; and (3) increased expression of sarcolemmal K(ATP) channels was observed following chronic training.
authors.affiliation: Department of Integrative Physiology, 202D Carlson Gymnasium, Campus Box 354, Boulder, CO 80309 USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Brown
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Chicco
authors.forename: Korinne N
authors.initials: KN
authors.lastname: Jew
authors.forename: Micah S
authors.initials: MS
authors.lastname: Johnson
authors.forename: Joshua M
authors.initials: JM
authors.lastname: Lynch
authors.forename: Peter A
authors.initials: PA
authors.lastname: Watson
authors.forename: Russell L
authors.initials: RL
authors.lastname: Moore
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D003652:Decanoic Acids / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D009206:Myocardium / Q000378:metabolism; D010805:Physical Conditioning, Animal; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011955:Receptors, Drug; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism*; D064233:Sulfonylurea Receptors; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control; D000099161:Kcnj11 Channel
chemical_list: D018528:ATP-Binding Cassette Transporters; D001549:Benzamides; D002118:Calcium; D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D020033:Protein Isoforms; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C117780:mitochondrial K(ATP) channel; C052853:5-hydroxydecanoic acid; C410297:HMR 1098