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Uncoupling of mitochondrial respiration by mK Ca channel activation is reduced in the older heart mitochondria
Author(s) -
Heinen Andre,
Winning Adrian,
Schlack Wolfgang,
Hollmann Markus W,
Preckel Benedikt,
Fraessdorf Jan,
HauckWeber Nina C
Publication year - 2007
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.21.6.a1225-c
Subject(s) - mitochondrion , respiration , potency , respiratory system , endocrinology , chemistry , medicine , biochemistry , in vitro , anatomy
The protective potency of ischemic preconditioning (IPC) decreases with increasing age. Furthermore, it is proposed that activation of mitochondrial Ca 2+ sensitive K + channels (mK Ca ) causes mild uncoupling of mitochondrial respiration, which is a key step in IPC. We hypothesized that aging reduces the effects of mK Ca opening on mitochondrial respiration. We measured effects of mK Ca opener NS1619 (30 μM) on O 2 consumption in isolated heart mitochondria from young (6–10 weeks) and old (22–26 months) Wistar rats under state 3 and state 4 conditions in the presence or absence of mK Ca blocker paxilline (5 μM). The respiratory control index (RCI) was calculated as state 3/state 4. p<0.05 vs. control ∗ , vs. NS1619 # In mitochondria from young rats, NS1619 increased state 4 by 11.9±4.1% ∗ , decreased state 3 by 7.6±2.5% ∗ , and reduced the RCI from 2.6±0.1 to 2.1±0.1 ∗ . Paxilline blocked the effect of NS1619 on state 4 (0.7±2.8% # ), did not reduce the decrease in state 3, and blunted the decrease of RCI from 2.1±0.1 to 2.3±0.1 # . In mitochondria from old rats, NS1619 had no effect on state 4 (0.4±2.0%), state 3 (−7.4±1.5%), and RCI (3.0±0.1). Increasing age reduced the effects of mK Ca opening on mitochondrial function. This could be one underlying mechanism of the decreased protective potency of IPC in the aged myocardium. (Funded by the research committee of the Heinrich‐Heine‐University Duesseldorf, Germany)