Premium
Activation of Mitochondrial Ca 2+ Sensitive Potassium Channels Enhances Mitochondrial Reactive Oxygen Species Production
Author(s) -
Heinen Andre,
Aldakkak Mohammed,
Camara Amadou KS,
Rhodes Samhita S,
Riess Matthias L,
Varadarajan Srinivasan G,
Stowe David F
Publication year - 2006
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.20.4.a315
Subject(s) - mitochondrion , reactive oxygen species , rotenone , mitochondrial ros , chemistry , respiration , biophysics , membrane potential , depolarization , oxygen , inner mitochondrial membrane , substrate (aquarium) , bioenergetics , biochemistry , biology , anatomy , ecology , organic chemistry
Preconditioning by activation of mitochondrial Ca 2+ sensitive K + channels (mK Ca ) protects the heart against ischemia/reperfusion injury. A role for altered mitochondrial bioenergetics and reactive oxygen species (ROS) to initiate this protection has been shown; however the underlying mechanism by which mK Ca opening causes ROS production to trigger preconditioning is unknown. We hypothesize that mK Ca opening causes ROS production due to differential changes in mitochondrial respiration and membrane potential (Φ m ). To test this we measured effects of mK Ca opener NS1619 on mitochondrial respiration, Φ m , and ROS generation. Guinea pig heart mitochondria were isolated and O 2 consumption (nmoles O 2 /min/mg protein), Φ m , and H 2 O 2 release were monitored in the presence of complex I substrate pyruvate (P) or complex II substrate succinate (+ complex I blocker rotenone, S/R). Data mean±SEM; *<0.05 NS1619 (30 μM) increased state 2 respiration from 17±1 (control) to 24±2* for P and from 60±2 (control) to 77±7* for S/R; these effects of NS1619 were abolished by 5 μM mK Ca blocker paxilline (19±1* for P, 63±3* for S/R). Φ m was not altered by NS1619 by either substrate but mitochondrial H 2 O 2 release increased by 55±5%* vs. control with S/R. In contrast, NS1619 did not increase H 2 O 2 release with P as substrate. K + influx into the mitochondrial matrix through mK Ca increases mitochondrial respiration, which in turn maintains Φ m . The increase in ROS production in S/R supported mitochondria is not caused by a depolarization of Φ m , but rather by increased respiration associated with maintained Φ m , conditions which can cause increased electron leak. (NIH)