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K ATP Channels are Important Downstream Targets of FGF2‐Initiated Cardioprotective Signaling in Mice
Author(s) -
Pietras Daniel Anthony,
Newman Gilbert,
Schultz Jo El Jean
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1130.9
Subject(s) - cardioprotection , ischemia , adenosine triphosphate , chemistry , ex vivo , ischemic preconditioning , pharmacology , reperfusion injury , medicine , endocrinology , microbiology and biotechnology , biochemistry , biology , in vitro
Our laboratory demonstrated that fibroblast growth factor‐2 (FGF2), a molecule whose vascular actions involve opening of surface adenosine triphosphate‐sensitive potassium (K ATP ) channels, confers resistance to ischemia‐reperfusion (I‐R) injury, a phenomenon termed cardioprotection. Other evidence indicates that K ATP channel opening, sarcolemmal or mitochondrial, is necessary for several modes of cardioprotection. Thus, our lab hypothesized that K ATP activation plays a major role in FGF2‐induced cardioprotection. Mouse hearts expressing a cardiospecific FGF2 transgene (Tg) and their nontransgenic (NTg) cohort were subjected to ex vivo global low‐flow I‐R. Hearts were treated before ischemia (isch) or before reperfusion (rep) with 10 μM sarcK ATP inhibitor (HMR1098) or before rep with 100 μM putative mitoK ATP inhibitor (5‐HD). Cell damage was assessed by creatine kinase (CK) release and infarct size was determined by triphenyltetrazolium chloride (TTC) staining. HMR1098 before isch or 5‐HD before rep demonstrated reduction of recovery in treated FGF2 Tg hearts vs. vehicle‐treated cohorts (p<0.05). 5‐HD also attenuated the FGF2‐induced decrease of infarct size and increased CK release from all hearts. Thus, sarcK ATP and mitoK ATP each participate in FGF2‐induced cardioprotection, but other effectors may also be involved.