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ASIC1a opposes exercise induced hyperemia and maximal exercise capacity
Author(s) -
Drummond Heather,
Gousset Monette,
AbuZaid Ahmed,
Daklallah Mohammed,
Weisman Jennifer,
Murphey Beau,
Hester Robert
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.924.7
Subject(s) - stimulation , medicine , extracellular , acid sensing ion channel , endocrinology , chemistry , vascular smooth muscle , cardiology , ion channel , biochemistry , receptor , smooth muscle
Acid Sensing Ion Channel 1a (ASIC1a) is an extracellular proton‐gated, cation‐selective channel in neurons and vascular smooth muscle cells (VSMC). It is unknown if ASIC1a contributes to vascular tone under conditions associated with extracellular acidosis, such as strenuous exercise. During exercise, vessel recruitment and dilation, mediated by the accumulation of extracellular protons, contribute to increases in blood flow to the exercising muscles. To determine if ASIC1a contributes to vascular responses during exercise, we measured femoral vascular conductance (FVC) during a step‐wise electrical stimulation (0.5 – 5.0 Hz at 3V for 60 sec) of the left major hindlimb muscle groups in anesthetized ASIC1a +/+ and ASIC1a −/− mice. Baseline hemodynamic parameters were similar. FVC increased to a greater extent in ASIC1a −/− versus ASIC1a +/+ mice (0.44 ± 0.03 vs. 0.30 ± 0.04 ml×min −1 ×100g hindlimb mass −1 , n=5 each, p=0.0009) with stimulation. The enhanced FVC was associated with a greater peak oxygen (O 2 ) uptake in conscious ASIC1a −/− mice during exhaustive treadmill running (9563 ± 120 vs. 8836 ± 276 ml×kg −1 ×hr −1 , n=6–7, p=0.0082). Differences in peak O 2 uptake were not due to differences in absolute or relative lean body mass. Our findings suggest ASIC1a activity may oppose increases in vascular conductance during strenuous exercise thus limiting peak exercise capacity. Supported by NHLBI 51971.