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  • Title: The effects of PGC-1α on control of microvascular P(O2) kinetics following onset of muscle contractions.
    Author: Kano Y, Miura S, Eshima H, Ezaki O, Poole DC.
    Journal: J Appl Physiol (1985); 2014 Jul 15; 117(2):163-70. PubMed ID: 24833782.
    Abstract:
    During contractions, regulation of microvascular oxygen partial pressure (Pmv(O2)), which drives blood-myocyte O2 flux, is a function of skeletal muscle fiber type and oxidative capacity and can be altered by exercise training. The kinetics of Pmv(O2) during contractions in predominantly fast-twitch muscles evinces a more rapid fall to far lower levels compared with slow-twitch counterparts. Peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) improves endurance performance, in part, due to mitochondrial biogenesis, a fiber-type switch to oxidative fibers, and angiogenesis in skeletal muscle. We tested the hypothesis that improvement of exercise capacity by genetic overexpression of PGC-1α would be associated with an altered Pmv(O2) kinetics profile of the fast-twitch (white) gastrocnemius during contractions toward that seen in slow-twitch muscles (i.e., slowed response kinetics and elevated steady-state Pmv(O2)). Phosphorescence quenching techniques were used to measure Pmv(O2) at rest and during separate bouts of twitch (1 Hz) and tetanic (100 Hz) contractions in gastrocnemius muscles of mice with overexpression of PGC-1α and wild-type littermates (WT) mice under isoflurane anesthesia. Muscles of PGC-1α mice exhibited less fatigue than WT (P < 0.01). However, except for the Pmv(O2) response immediately following onset of contractions, WT and PGC-1α mice demonstrated similar Pmv(O2) kinetics. Specifically, the time delay of the Pmv(O2) response was shortened in PGC-1α mice compared with WT (1 Hz: WT, 6.6 ± 2.4 s; PGC-1α, 2.9 ± 0.8 s; 100 Hz: WT, 3.3 ± 1.1 s, PGC-1α, 0.9 ± 0.3 s, both P < 0.05). The ratio of muscle force to Pmv(O2) was higher for the duration of tetanic contractions in PGC-1α mice. Slower dynamics and maintenance of higher Pmv(O2) following muscle contractions is not obligatory for improved fatigue resistance in fast-twitch muscle of PGC-1α mice. Moreover, overexpression of PGC-1α may accelerate O2 utilization kinetics to a greater extent than O2 delivery kinetics.
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