title: Cardioprotection by K(ATP) channels in wild-type hearts and hearts overexpressing A(1)-adenosine receptors.
abstract: We studied the role of mitochondrial ATP-sensitive K(+) (K(ATP)) channels in modifying functional responses to 20 min global ischemia and 30 min reperfusion in wild-type mouse hearts and in hearts with approximately 250-fold overexpression of functionally coupled A(1)-adenosine receptors (A(1)ARs). In wild-type hearts, time to onset of contracture (TOC) was 303 +/- 24 s, with a peak contracture of 89 +/- 5 mmHg. Diastolic pressure remained elevated at 52 +/- 6 mmHg after reperfusion, and developed pressure recovered to 40 +/- 6% of preischemia. A(1)AR overexpression markedly prolonged TOC to 517 +/- 84 s, reduced contracture to 64 +/- 6 mmHg, and improved recovery of diastolic (to 9 +/- 4 mmHg) and developed pressure (to 82 +/- 8%). 5-Hydroxydecanoate (5-HD; 100 microM), a mitochondrial K(ATP) blocker, did not alter ischemic contracture in wild-type hearts, but increased diastolic pressure to 69 +/- 8 mmHg and reduced developed pressure to 10 +/- 5% during reperfusion. In transgenic hearts, 5-HD reduced TOC to 348 +/- 18 s, increased postischemic contracture to 53 +/- 4 mmHg, and reduced recovery of developed pressure to 22 +/- 4%. In summary, these data are the first to demonstrate that endogenous activation of K(ATP) channels improves tolerance to ischemia-reperfusion in murine myocardium. This functional protection occurs without modification of ischemic contracture. The data also support a role for mitochondrial K(ATP) channel activation in the pronounced cardioprotection afforded by overexpression of myocardial A(1)ARs.
authors.affiliation: The Rotary Centre for Cardiovascular Research, Griffith University Gold Coast Campus, Southport, QLD 4217 Australia. j.headrick@mailbox.gu.edu.au
authors.forename: J P
authors.initials: JP
authors.lastname: Headrick
authors.forename: N S
authors.initials: NS
authors.lastname: Gauthier
authors.forename: R
authors.initials: R
authors.lastname: Morrison
authors.forename: G P
authors.initials: GP
authors.lastname: Matherne
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D008929:Mitochondria, Heart / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology*; D018047:Receptors, Purinergic P1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012016:Reference Values; D013997:Time Factors
chemical_list: D003652:Decanoic Acids; D006880:Hydroxy Acids; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D018047:Receptors, Purinergic P1; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate