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 ameliorat e biochemical and morphological impairment upon succeeding severe isch emia. We investigated whether the pattern of respiratory enzyme activi ty (RA), adeninenucleotides, and membrane potential in hippocampal sli ces following low-dose in vivo (20 mg/kg) and high-dose in vitro (1 mM ) application of 3-nitropropionic acid (3-np), a specific inhibitor of succinic dehydrogenase (SDH), indicates a similar tolerance phenomeno n. One hour in vivo treatment decreased RA, spectrophotometrically qua ntitated by intensity of staining with 2,3,5-triphenyltetrazolium chlo ride (TTC), to 48 +/- 5%(mean a SE; P < 0.01). Intermittent increase a fter 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 (CA1(SP)) vs CA3 (CA3(SP )) (89 +/- 6% vs 57 +/- 6% of control; P < 0.01). ATP levels parallele d the intensity of average (CA1(SP), CA3(SP), plus CA1 stratum radiatu m) TTC staining (r = 0.93), After pretreatment with 3-np in vivo for 1 h, no further decrease of RA upon 30-min in vitro treatment was seen in any region. At all other times, RA declined further upon in vitro t reatment (P < 0.01). Compared to I-h in vivo treatment, hyperpolarizat ion of CA1(SP) pyramidal cells upon in vitro application of 1 mM 3-np was reduced after 8-h pretreatment in vivo (P < 0.04). At this time, d epolarization upon glibenclamide (10 mu M), an antagonist at K-ATP-cha nnels, was reduced. We conclude that the severity of impairment of oxi dative phosphorylation upon repeated inhibition of SDH in vivo and in vitro is not increased in an additive manner. At appropriate times, re lative protection against further decrease of energy metabolism is obs erved - chemical preconditioning. Activation of K-ATP-channels is asso ciated with chemical preconditioning. (C) 1996 Academic Press, Inc.