Abstract
Vascular smooth muscle cells in resistance arterioles express a diverse array of ion channels that control microvascular function. Specifically, voltage-dependent potassium (KV) channels induce vasodilation via smooth muscle hyperpolarization, positioning these channels as important regulators of vascular tone, and thus blood flow. PURPOSE: Despite substantial research exploring the influence of KV channels in the regulation of blood flow in various animal models, many aspects of their regulation remain incompletely understood in humans. Specifically, this relationship has never been explored in human skeletal muscle in vivo, the major site of total peripheral resistance. Therefore, we tested the hypothesis that KV channel inhibition would attenuate endothelium-dependent and endothelium-independent vasodilation in skeletal muscle of humans. METHODS: We utilized skeletal muscle microdialysis to bypass the cutaneous circulation and directly measure the local hyperemic response to methacholine (55 mM; endothelium-dependent) and sodium nitroprusside (42 mM; endothelial-independent) in the vastus lateralis muscle of 15 healthy adults (5 women, 28 ± 4 yrs). At separate sites, the 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. RESULTS: Baseline blood flow did not differ between control (16.3 ± 10.2 ml • min-1 • 100g-1) and 4-aminopyridine (17.2 ± 8.6 ml • min-1 • 100g-1) sites (P = 0.7). However, the hyperemic response to methacholine (Δ 30.2 ± 12.1 ml • min-1 • 100g-1) was attenuated when co-infused with 4-aminopyridine (Δ 4.6 ± 10.1 ml • min-1 • 100g-1; P < 0.01). Similarly, the hyperemic response to sodium nitroprusside was reduced when co-infused with 4-aminopyridine (sodium nitroprusside alone, Δ 60.8 ± 27.2 ml • min-1 • 100g-1 vs. sodium nitroprusside + 4-aminopyridine, Δ 14.6 ± 11.1 ml • min-1 • 100g-1; P < 0.01). CONCLUSION: These data suggest that KV channel antagonism attenuates endothelium-dependent vasodilation in skeletal muscle of humans. Further, our observation that KV channel antagonism similarly reduced endothelium-independent dilation suggests that KV channels may function as an end-target of the nitric oxide-cyclic guanosine monophosphate-protein kinase G signaling pathway.
Recommended Citation
Ruiz-Pick, Ysabella I.; Richey, Rauchelle E.; Gilliland, Brenda L.; Garfield, Tyson C.; Kichloo, Asim; Olivencia-Yurvati, Albert H.; Dick, Gregory M.; and Romero, Steven A.
(2025)
"Effect of Voltage-Dependent Potassium Channel Antagonism on Vasodilation in Skeletal Muscle of Humans,"
International Journal of Exercise Science: Conference Proceedings: Vol. 2:
Iss.
17, Article 4.
Available at:
https://digitalcommons.wku.edu/ijesab/vol2/iss17/4
