Abstract
The protective potency of ischemic preconditioning (IPC) decreases with increasing age. Furthermore, it is proposed that activation of mitochondrial Ca2+ sensitive K+ channels (mKCa) causes mild uncoupling of mitochondrial respiration, which is a key step in IPC. We hypothesized that aging reduces the effects of mKCa opening on mitochondrial respiration. We measured effects of mKCa opener NS1619 (30 μM) on O2 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 mKCa 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 mKCa 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)
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