Open AccessEnhanced maximal exercise capacity, vasodilation to electrical muscle contraction, and hind limb vascular density in ASIC1a null mice
Author(s) -
Drummond Heather A.,
Xiang Lusha,
Chade Alejandro R.,
Hester Robert
Publication year - 2017
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.13368
Subject(s) - vasodilation , hindlimb , vascular smooth muscle , extracellular , acid sensing ion channel , medicine , contraction (grammar) , endocrinology , vasoconstriction , chemistry , anatomy , ion channel , biochemistry , receptor , smooth muscle
Acid‐sensing ion channel ( ASIC ) proteins form extracellular proton‐gated, cation‐selective channels in neurons and vascular smooth muscle cells and are proposed to act as extracellular proton sensors. However, their importance to vascular responses under conditions associated with extracellular acidosis, such as strenuous exercise, is unclear. Therefore, the purpose of this study was to determine if one ASIC protein, ASIC 1a, contributes to extracellular proton‐gated vascular responses and exercise tolerance. To determine if ASIC 1a contributes to exercise tolerance, we determined peak oxygen (O 2 ) uptake in conscious ASIC 1a −/− mice during exhaustive treadmill running. Loss of ASIC 1a was associated with a greater peak running speed (60 ± 2 vs. 53 ± 3 m·min −1 , P = 0.049) and peak oxygen (O 2 ) uptake during exhaustive treadmill running (9563 ± 120 vs. 8836 ± 276 mL·kg −1 ·h −1 , n = 6–7, P = 0.0082). There were no differences in absolute or relative lean body mass, as determined by EchoMRI. To determine if ASIC 1a contributes to vascular responses during muscle contraction, we measured femoral vascular conductance ( FVC ) during a stepwise electrical stimulation (0.5–5.0 Hz at 3 V for 60 sec) of the left major hind limb muscles. FVC increased to a greater extent in ASIC 1a −/− versus ASIC 1a +/+ mice (0.44 ± 0.03 vs. 0.30 ± 0.04 mL·min −1 ·100 g hind limb mass −1 · mmHg −1 , n = 5 each, P = 0.0009). Vasodilation following local application of external protons in the spinotrapezius muscle increased the duration, but not the magnitude, of the vasodilatory response in ASIC 1a −/− mice. Finally, we examined hind limb vascular density using micro‐ CT and found increased density of 0–80 μ m vessels ( P < 0.05). Our findings suggest an increased vascular density and an enhanced vasodilatory response to local protons, to a lesser degree, may contribute to the enhanced vascular conductance and increased peak exercise capacity in ASIC 1a −/− mice.