Voltage-dependent potassium channels and vasodilation in skeletal muscle of humans: impact of age

We recently identified a critical role for voltage-dependent potassium (KV) channels in the vasodilation induced by methacholine and sodium nitroprusside in skeletal muscle of young humans. Despite several animal studies suggesting that KV channel-dependent vasodilation is altered in primary aging, this relationship has never been explored in aged humans. Therefore, we tested the hypothesis that KV channel antagonism would attenuate the hyperemic response to methacholine and sodium nitroprusside to a lesser extent in aged adults, when compared to their young counterparts. We utilized skeletal muscle microdialysis to directly measure the local hyperemic response to methacholine (55 mM) and sodium nitroprusside (42 mM) in the vastus lateralis muscle of 5 aged adults (4 postmenopausal women, 66 ± 7 yrs) and 17 young adults (7 premenopausal women, 28 ± 4 yrs). At separate sites, the non-selective KV channel antagonist, 4-aminopyridine (26.6 mM), was co-infused with each vasodilator substance. Local skeletal muscle blood flow was assessed using the ethanol washout technique. Primary outcomes were analyzed using a two-way (group x probe) linear mixed model ANOVA with repeated measures. Baseline blood flow did not differ between control (young, 16 ± 9 ml min-1 100 g-1 vs. aged, 15 ± 10 ml min-1 100 g-1) and 4-aminopyridine sites (young, 18 ± 8 ml min-1 100 g-1 vs. aged, 19 ± 8 ml min-1 100 g-1; P = 0.6). The hyperemic response to methacholine (young, Δ 28 ± 12 ml min-1 100 g-1 vs. aged, Δ 20 ± 13 ml min-1 100 g-1) was abolished when co-infused with 4-aminopyridine (young, Δ 3 ± 9 ml min-1 100 g-1 vs. aged, Δ 4 ± 12 ml min-1 100 g-1), an effect that did not differ between age groups (P = 0.3 for interaction). Similarly, the magnitude by which 4-aminopyridine reduced the hyperemic response to sodium nitroprusside did not differ between age groups (young, Δ 59 ± 27 to 14 ± 10 ml min-1 100 g-1; aged: Δ 50 ± 8 to 12 ± 4 ml min-1 100 g-1; P = 0.6 for interaction). These preliminary data suggest that KV channel-dependent vasodilation persists in skeletal muscle across the adult lifespan. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.