MiPsummer Programme pdf - Mitochondrial Physiology Society

31
Abstract # 5
The progressive effects of exercise training on the acute regulation of creatine-independent
respiratory sensitivity to ADP in human skeletal muscle
M. Ydfors 1 , M. Hughes 2 , R. Laham 2 , J. Norrbom 1 , and C.G.R. Perry 2 .
1 Department of Physiology & Pharmacology, Karolinska Institutet, Stockholm Sweden
2 Muscle Health Research Centre, York University, Toronto, ON, Canada.
Background: Creatine-independent regulation of apparent mitochondrial respiratory sensitivity
(K mapp ) to ADP is thought to occur through diffusion of adenine nucleotides between the cytoplasm
and mitochondrial matrix via specific membrane transporters. While creatine-dependent phosphate
shuttling was demonstrated to be regulated by in situ contraction of permeabilized muscle fibres 1
and exercise in humans 2 , creatine-independent K mapp to ADP became impaired following moderate
intensity exercise 2 . This surprise deficiency would appear to be a limitation to maintaining energy
homeostasis during exercise and may therefore be subject to improvement with continual exercise
challenges.
Objectives: To determine the progressive effects of exercise training on the response of creatineindependent
K mapp to acute exercise challenges in human skeletal muscle.
Methods: High-resolution respirometry (Oroboros, Oxygraph-2k) was used to determine K mapp to
ADP (Complex I-supported ADP titrations) in relaxed (25uM Blebbistatin, a myosin II ATPase
inhibitor 1,2 ) permeabilized muscle fibres at 37 C prepared from human vastus lateralis biopsies
sampled Pre, immediately Post and 3hr-Post exercise (1hr, 10 x 4 min intervals of cycling at 91%
maximum heart rate separated by 2 min rest) in ten healthy but un-trained men (age, body weight
and VO 2 peak were 24+/- 1 yr, 74.6 +/- 3.5 kg, 52.1 +/- 1.9 ml/kg/min respectively). Participants
then completed eight additional exercise sessions with the biopsy trial repeated at the 5 th and 9 th
session.
Results: K mapp to ADP was quite insensitive pre-training (Pre, 687 µM) but improved following the
1 st exercise challenge (Post, 478 µM, p