Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle
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) r...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-04-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.14803 |
| _version_ | 1819134036329627648 |
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| author | Daniel M. Hirai Ayaka Tabuchi Jesse C. Craig Trenton D. Colburn Timothy I. Musch David C. Poole |
| author_facet | Daniel M. Hirai Ayaka Tabuchi Jesse C. Craig Trenton D. Colburn Timothy I. Musch David C. Poole |
| author_sort | Daniel M. Hirai |
| collection | DOAJ |
| description | 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 (DO2m). 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∝DO2m/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. |
| first_indexed | 2024-12-22T09:56:48Z |
| format | Article |
| id | doaj.art-b20fc1fe65d3480a9d137669e6ded96e |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-22T09:56:48Z |
| publishDate | 2021-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-b20fc1fe65d3480a9d137669e6ded96e2022-12-21T18:30:14ZengWileyPhysiological Reports2051-817X2021-04-0198n/an/a10.14814/phy2.14803Regulation of capillary hemodynamics by KATP channels in resting skeletal muscleDaniel M. Hirai0Ayaka Tabuchi1Jesse C. Craig2Trenton D. Colburn3Timothy I. Musch4David C. Poole5Department of Health and Kinesiology Purdue University West Lafayette Indiana USADepartment of Kinesiology Kansas State University Manhattan Kansas USADepartment of Kinesiology Kansas State University Manhattan Kansas USADepartment of Kinesiology Kansas State University Manhattan Kansas USADepartment of Kinesiology Kansas State University Manhattan Kansas USADepartment of Kinesiology Kansas State University Manhattan Kansas USAAbstract 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 (DO2m). 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∝DO2m/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.https://doi.org/10.14814/phy2.14803ATP‐sensitive K+ channelblood flowintravital microscopymicrocirculationred blood cell |
| spellingShingle | Daniel M. Hirai Ayaka Tabuchi Jesse C. Craig Trenton D. Colburn Timothy I. Musch David C. Poole Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle Physiological Reports ATP‐sensitive K+ channel blood flow intravital microscopy microcirculation red blood cell |
| title | Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle |
| title_full | Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle |
| title_fullStr | Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle |
| title_full_unstemmed | Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle |
| title_short | Regulation of capillary hemodynamics by KATP channels in resting skeletal muscle |
| title_sort | regulation of capillary hemodynamics by katp channels in resting skeletal muscle |
| topic | ATP‐sensitive K+ channel blood flow intravital microscopy microcirculation red blood cell |
| url | https://doi.org/10.14814/phy2.14803 |
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