Regulation of capillary hemodynamics by K channels in resting skeletal muscle.

ATP-sensitive K channels (K ) have been implicated in the regulation of resting vascular smooth muscle membrane potential and tone. However, whether K channels modulate skeletal muscle microvascular hemodynamics at the capillary level (the primary site for blood-myocyte O exchange) remains unknown. We tested the hypothesis that K 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 (f ), velocity (V ), and capillary tube hematocrit (Hct ) were assessed via intravital microscopy of the rat spinotrapezius muscle (n = 6) under control (CON) and glibenclamide (GLI; K 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 f (CON:20.1 ± 1.8, GLI:14.6 ± 1.3 cells/s; p < 0.05) and V (CON:240 ± 17, GLI:182 ± 17 µm/s; p < 0.05) but not Hct (CON:0.26 ± 0.01, GLI:0.26 ± 0.01; p > 0.05). The absence of GLI effects on the %RBC-flowing capillaries and Hct indicates preserved muscle O diffusing capacity (DO m). In contrast, GLI lowered both f and V thus impairing perfusive microvascular O transport (Q̇m) and lengthening RBC capillary transit times, respectively. Given the interdependence between diffusive and perfusive O conductances (i.e., %O extraction∝DO m/Q̇m), such GLI alterations are expected to elevate muscle %O extraction to sustain a given metabolic rate. These results support that K channels regulate capillary hemodynamics and, therefore, microvascular gas exchange in resting skeletal muscle.