Mitochondrial Oxidation in Rat Hippocampus Can Be Preconditioned by Selective Chemical Inhibition of Succinic Dehydrogenase

Repeatedly it was reported that a short ischemic episode may ameliorate biochemical and morphological impairment upon succeeding severe ischemia. We investigated whether the pattern of respiratory enzyme activity (RA), adeninenucleotides, and membrane potential in hippocampal slices following low-dosein vivo(20 mg/kg) and high-dosein vitro(1 mM) application of 3-nitropropionic acid (3-np), a specific inhibitor of succinic dehydrogenase (SDH), indicates a similar tolerance phenomenon. One hourin vivotreatment decreased RA, spectrophotometrically quantitated by intensity of staining with 2,3,5-triphenyltetrazolium chloride (TTC), to 48 ± 5% (mean±SE;P<0.01). Intermittent increase after 2 h (79±5%;P<0.05) was followed by gradual decline to 48 ± 16% (P<0.01) after 8 h. The intermittent increase predominated in stratum pyramidale of hippocampal region CA1 (CA1SP) vs CA3 (CA3SP) (89±6% vs 57±6% of control;P<0.01). ATP levels paralleled the intensity of average (CA1SP, CA3SP, plus CA1 stratum radiatum) TTC staining (r=0.93). After pretreatment with 3-npin vivofor 1 h, no further decrease of RA upon 30-minin vitrotreatment was seen in any region. At all other times, RA declined further uponin vitrotreatment (P<0.01). Compared to 1-hin vivotreatment, hyperpolarization of CA1SPpyramidal cells uponin vitroapplication of 1 mM3-np was reduced after 8-h pretreatmentin vivo(P<0.04). At this time, depolarization upon glibenclamide (10 μM), an antagonist at KATP-channels, was reduced. We conclude that the severity of impairment of oxidative phosphorylation upon repeated inhibition of SDHin vivoandin vitrois not increased in an additive manner. At appropriate times, relative protection against further decrease of energy metabolism is observed—chemical preconditioning. Activation of KATP-channels is associated with chemical preconditioning.