Premium
Differential effects of small and big Ca 2+ ‐sensitive K + channel agonists and antagonists during cardiac ischemia and reperfusion injury (648.10)
Author(s) -
Stowe David,
Yang Meiying,
Schwabe David,
Heisner James,
Camara Amadou
Publication year - 2014
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.28.1_supplement.648.10
Subject(s) - chemistry , ischemia , in vivo , bk channel , pharmacology , channel blocker , reperfusion injury , repolarization , anesthesia , medicine , membrane potential , calcium , biochemistry , electrophysiology , biology , microbiology and biotechnology , organic chemistry
Small and big conductance Ca 2+ ‐sensitive K + channel (SK Ca , BK Ca ) agonists have been shown to provide preconditioning protection against cardiac ischemia reperfusion (IR) injury. We tested if activation or block of SK Ca vs . BK Ca channels, initiated before ischemia through initial reperfusion, differently reduce or worsen cardiac global IR injury in isolated rodent hearts, and if these drugs are effective if given IV in vivo before and during regional (LAD) coronary artery occlusion. We found that activating SK Ca or BK Ca channels by DCEB or NS1619 reduced infarct size (IS) after 35 min of ischemia by 26 and 39% in vivo, and by 56 and 62% in vitro vs. IR alone respectively; BK Ca and SK Ca blockers paxilline+NS8593, respectively, increased IS by 17% in vivo and by 30% in vitro vs. IR alone. In vitro the two agonists also increased LVP by 90 and 88% and the blockers reduced it by 45% vs. IR alone. Activation of SK Ca and BK Ca channels improved the respiratory control index (state3/4), increased Ca 2+ retention capacity, and restored membrane repolarization in mitochondria isolated after IR. Our results show similar effects of these drugs when given in vivo or in vitro indicating their bioavailability in the heart when given IV. Since each of SK Ca ‐ BK Ca agonists/antagonists exert effects on isolated cardiac mitochondria, our data also suggest that activation of K Ca channels endogenously protects against cardiac injury in part by improving mitochondrial function. Grant Funding Source : R01 HL 089514