Key result
Prolonged ischemia in rat skeletal muscle reduced maximal SR Ca2+-ATPase activity to 73% of double control levels (P<0.05), associated with a 26% reduction in FITC binding capacity.
Absolute Event Rate: 11609% vs 17562%
p-value: p=<0.05
Prolonged ischemia in skeletal muscle reduces maximal SR Ca2+-ATPase activity, likely due to structural modifications in the nucleotide binding domain.
Hypothesis-generating for SR Ca2+-ATPase impairment in ischemia; leaves open relevance to human peripheral artery disease.
In this study, we employed an in vivo model of prolonged ischemia in rat skeletal muscle to investigate the hypothesis that structural modifications to the sarcoplasmic reticulum (SR) Ca2+-ATPase can explain the alterations in Ca2+-ATPase activity that occur with ischemia. To induce total ischemia, a tourniquet was placed around the upper hindlimb in 27 female Sprague-Dawley rats weighing 256 +/- 6.7 g (mean +/- SE) and was inflated to 350 mmHg for 4 h. The contralateral limb served as control (C) to the ischemic limb (I), and the limbs of animals killed immediately after anesthetization served as a double control (CC). Mixed gastrocnemius and tibialis anterior muscles were sampled and used for SR vesicle preparation. Maximal Ca2+-ATPase activity (micromol x g protein(-1) x min(-1)) of C (15,802 +/- 1,246) and I (11,609 +/- 1,029) was 90 and 73% (P < 0.05) of CC (17,562 +/- 1,682), respectively. No differences were found between groups in either the Hill coefficient or the free Ca2+ at half-maximal activity. The fluorescent probes, FITC and N-cyclohexyl-N'-(dimethylamino-alpha-naphthyl) carbodiimide, used to assess structural alterations in the regions of the ATP binding site and the Ca2+ binding sites of the Ca2+-ATPase, respectively, indicated a 26% reduction (P < 0.05) in FITC binding capacity (absolute units) in I (0.22 +/- 0.01) compared with CC (0.29 +/- 0.02) and C (0.29 +/- 0.03). Our results suggest that the reduction in maximal SR Ca2+-ATPase activity in SR vesicles with ischemia is related to structural modification in the region of the nucleotide binding domain by mechanisms that are as yet unclear.
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Tupling et al. (2001) studied Ischemia (n=27). Prolonged ischemia vs. Contralateral limb (control) and double control was evaluated on Maximal Ca2+-ATPase activity (micromol x g protein(-1) x min(-1)) (p=<0.05). Prolonged ischemia in rat skeletal muscle reduced maximal SR Ca2+-ATPase activity to 73% of double control levels (P<0.05), associated with a 26% reduction in FITC binding capacity.
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