The effects of PGC-1α on control of microvascular Po2 kinetics following onset of muscle contractions

Abstract

During contractions, regulation of microvascular oxygen partial pressure (Pmvo2), 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 Pmvo2 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 Pmvo2 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 Pmvo2). Phosphorescence quenching techniques were used to measure Pmvo2 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 Pmvo2 response immediately following onset of contractions, WT and PGC-1α mice demonstrated similar Pmvo2 kinetics. Specifically, the time delay of the Pmvo2 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 Pmvo2 was higher for the duration of tetanic contractions in PGC-1α mice. Slower dynamics and maintenance of higher Pmvo2 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.