KIR channel activation links local vasodilatation with muscle fibre recruitment during exercise in humans

Key points During exercise, blood flow to working skeletal muscle increases in parallel with contractile activity such that oxygen delivery is sufficient to meet metabolic demand. K+ released from active skeletal muscle fibres could facilitate vasodilatation in proportion to the degree of muscle fibre recruitment. Once released, K+ stimulates inwardly rectifying K+ (K-IR) channels on the vasculature to elicit an increase in blood flow. In the present study, we demonstrate that K-IR channels mediate the rapid vasodilatory response to an increase in exercise intensity. We also show that K-IR channels augment vasodilatation during exercise which demands greater muscle fibre recruitment independent of the total amount of work performed. These results suggest that K+ plays a key role in coupling the magnitude of vasodilatation to the degree of contractile activity. Ultimately, the findings from this study help us understand the signalling mechanisms that regulate muscle blood flow in humans. Blood flow to active skeletal muscle is augmented with greater muscle fibre recruitment. We tested whether activation of inwardly rectifying potassium (K-IR) channels underlies vasodilatation with elevated muscle fibre recruitment when work rate is increased (Protocol 1) or held constant (Protocol 2). We assessed forearm vascular conductance (FVC) during rhythmic handgrip exercise under control conditions and during local inhibition of K-IR channels (intra-arterial BaCl2). In Protocol 1, healthy volunteers performed mild handgrip exercise for 3 min, then transitioned to moderate intensity for 30 s. BaCl2 eliminated vasodilatation during the first contraction at the moderate workload (Delta FVC, BaCl2: -1 +/- 17 vs. control: 30 +/- 28 ml min(-1) 100 mmHg(-1); n = 9; P = 0.004) and attenuated the 30 s area under the curve by 56 +/- 14% (n = 9; P < 0.0001). In Protocol 2, participants performed two exercise bouts in which muscle fibre recruitment was manipulated while total contractile work was held constant via reciprocal changes in contraction frequency: (1) low fibre recruitment, with contractions at 12.5% maximal voluntary contraction once every 4 s and (2) high fibre recruitment, with contractions at 25% maximal voluntary contraction once every 8 s. Under control conditions, steady-state FVC was augmented in high vs. low fibre recruitment (211 +/- 90 vs. 166 +/- 73 ml min(-1).100 mmHg(-1); n = 10; P = 0.0006), whereas BaCl2 abolished the difference between high and low fibre recruitment (134 +/- 59 vs. 134 +/- 63 ml min(-1) 100 mmHg(-1); n = 10; P = 0.85). These findings demonstrate that K-IR channel activation is a key mechanism linking local vasodilatation with muscle fibre recruitment during exercise.