Functional characterisation and subcellular localisation of HCN1 channels in rabbit retinal rod photoreceptors

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Abstract
We have used a constant [1,2-13C]acetate infusion (0.12 μmol min−1 kg1) for 2 h at rest, followed by 2 h of one-legged knee-extensor exercise at 65 % of leg maximal workload, and 3 h of recovery in six post-absorptive volunteers to quantify whole-body and leg acetate kinetics and determine whether the whole-body acetate correction factor can be used to correct leg substrate oxidation. The acetate whole-body rate of appearance (Ra) was not significantly different at rest, during exercise or during recovery (365-415 μmol min−1). The leg net acetate uptake was similar at rest and during recovery (≈10 μmol min−1), but increased ∼5-fold with exercise. At rest the leg acetate uptake (≈15 μmol min−1) and release (≈5 μmol min−1) accounted for 4 and 1.5 % of whole-body acetate disposal (Rd) and Ra, respectively. When the leg acetate kinetics were extrapolated to the total body skeletal muscle mass, then skeletal muscle accounted for ∼16 and ∼6 % of acetate Rd and Ra. With exercise, leg acetate uptake increased ∼6-fold, whereas leg acetate release increased 9-fold compared with rest. Whole-body acetate carbon recovery increased with time of infusion at rest and during recovery from 21 % after 1.5 h of infusion to 45 % in recovery after 7 h of infusion. Leg and whole-body acetate carbon recovery were similar under resting conditions, both before and after exercise. During exercise whole-body acetate carbon recovery was ∼75 %, however, acetate carbon recovery of the active leg was substantially higher (≈100 %). It is concluded that inactive skeletal muscle plays a minor role in acetate turnover. However, active skeletal muscle enhances several-fold acetate uptake and subsequent oxidation, as well as release and its contribution to whole-body acetate turnover. Furthermore, under resting conditions the whole-body acetate correction factor can be used to correct for leg, skeletal muscle, substrate oxidation, but not during exercise.