Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr;9(8):e14803.
doi: 10.14814/phy2.14803.

Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle

Daniel M Hirai  1   2 , Ayaka Tabuchi  2   3 , Jesse C Craig  2   4   5 , Trenton D Colburn  2 , Timothy I Musch  2   6 , David C Poole  2   6
Affiliations

Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle

Daniel M Hirai et al. Physiol Rep. 2021 Apr.

Abstract

ATP-sensitive K+ channels (KATP ) have been implicated in the regulation of resting vascular smooth muscle membrane potential and tone. However, whether KATP channels modulate skeletal muscle microvascular hemodynamics at the capillary level (the primary site for blood-myocyte O2 exchange) remains unknown. We tested the hypothesis that KATP channel inhibition would reduce the proportion of capillaries supporting continuous red blood cell (RBC) flow and impair RBC hemodynamics and distribution in perfused capillaries within resting skeletal muscle. RBC flux (fRBC ), velocity (VRBC ), and capillary tube hematocrit (Hctcap ) were assessed via intravital microscopy of the rat spinotrapezius muscle (n = 6) under control (CON) and glibenclamide (GLI; KATP channel antagonist; 10 µM) superfusion conditions. There were no differences in mean arterial pressure (CON:120 ± 5, GLI:124 ± 5 mmHg; p > 0.05) or heart rate (CON:322 ± 32, GLI:337 ± 33 beats/min; p > 0.05) between conditions. The %RBC-flowing capillaries were not altered between conditions (CON:87 ± 2, GLI:85 ± 1%; p > 0.05). In RBC-perfused capillaries, GLI reduced fRBC (CON:20.1 ± 1.8, GLI:14.6 ± 1.3 cells/s; p < 0.05) and VRBC (CON:240 ± 17, GLI:182 ± 17 µm/s; p < 0.05) but not Hctcap (CON:0.26 ± 0.01, GLI:0.26 ± 0.01; p > 0.05). The absence of GLI effects on the %RBC-flowing capillaries and Hctcap indicates preserved muscle O2 diffusing capacity (DO2 m). In contrast, GLI lowered both fRBC and VRBC thus impairing perfusive microvascular O2 transport (Q̇m) and lengthening RBC capillary transit times, respectively. Given the interdependence between diffusive and perfusive O2 conductances (i.e., %O2 extraction∝DO2 m/Q̇m), such GLI alterations are expected to elevate muscle %O2 extraction to sustain a given metabolic rate. These results support that KATP channels regulate capillary hemodynamics and, therefore, microvascular gas exchange in resting skeletal muscle.

Keywords: ATP-sensitive K+ channel; blood flow; intravital microscopy; microcirculation; red blood cell.

PubMed Disclaimer

Conflict of interest statement

No conflicts of interest, financial or otherwise, are declared by the authors.

Figures

FIGURE 1
FIGURE 1
Percentage of capillaries supporting red blood cell (RBC) flow during control (CON; n = 6) and KATP channel inhibition (glibenclamide, GLI; n = 6) conditions. Dashed lines represent individual muscle data
FIGURE 2
FIGURE 2
Capillary red blood cell flux (top panel) and velocity (bottom panel) during control (CON; n = 6) and KATP channel inhibition (glibenclamide, GLI; n = 6) conditions. Dashed lines represent individual muscle data. *p < 0.05 vs. CON
FIGURE 3
FIGURE 3
Relative frequency histograms of capillary red blood cell flux (top panel) and velocity (bottom panel) during control (CON; n = 6) and KATP channel inhibition (glibenclamide, GLI; n = 6) conditions. Arrows show mean values. *p < 0.05 vs. CON
FIGURE 4
FIGURE 4
Individual and mean capillary relationships (top and bottom panels, respectively) between red blood cell flux and velocity during control (CON) and KATP channel inhibition (glibenclamide, GLI) conditions. Each data point represents a single capillary in the top panel (n = 30) and the average value for all capillaries within a single muscle (n = 6) in the bottom panel
See this image and copyright information in PMC

References

    1. Altman, P. , & Dittmer, D. (1974). Biology data book, 2nd ed. Federation of American Societies for Experimental Biology.
    1. Bailey, J. K. , Kindig, C. A. , Behnke, B. J. , Musch, T. I. , Schmid‐Schoenbein, G. W. , & Poole, D. C. (2000). Spinotrapezius muscle microcirculatory function: Effects of surgical exteriorization. American Journal of Physiology. Heart and Circulatory Physiology, 279, H3131–3137. 10.1152/ajpheart.2000.279.6.H3131. - DOI - PubMed
    1. Bank, A. J. , Sih, R. , Mullen, K. , Osayamwen, M. , & Lee, P. C. (2000). Vascular ATP‐dependent potassium channels, nitric oxide, and human forearm reactive hyperemia. Cardiovascular Drugs and Therapy, 14, 23–29. 10.1023/a:1007835003493. - DOI - PubMed
    1. Berg, B. R. , & Sarelius, I. H. (1996). Erythrocyte flux in capillary networks during maturation: Implications for oxygen delivery. American Journal of Physiology, 271, H2263–2273. 10.1152/ajpheart.1996.271.6.H2263. - DOI - PubMed
    1. Cohen, K. D. , Berg, B. R. , & Sarelius, I. H. (2000). Remote arteriolar dilations in response to muscle contraction under capillaries. American Journal of Physiology. Heart and Circulatory Physiology, 278, H1916–1923. 10.1152/ajpheart.2000.278.6.H1916. - DOI - PubMed

Publication types

LinkOut - more resources