Sarcolemmal ATP-sensitive potassium channels modulate skeletal muscle function under low-intensity workloads

ATP-sensitive potassium (K(ATP)) channels have the unique ability to adjust membrane excitability and functions in accordance with the metabolic status of the cell. Skeletal muscles are primary sites of activity-related energy consumption and have K(ATP) channels expressed in very high density. Previously, we demonstrated that transgenic mice with skeletal muscle–specific disruption of K(ATP) channel function consume more energy than wild-type littermates. However, how K(ATP) channel activation modulates skeletal muscle resting and action potentials under physiological conditions, particularly low-intensity workloads, and how this can be translated to muscle energy expenditure are yet to be determined. Here, we developed a technique that allows evaluation of skeletal muscle excitability in situ, with minimal disruption of the physiological environment. Isometric twitching of the tibialis anterior muscle at 1 Hz was used as a model of low-intensity physical activity in mice with normal and genetically disrupted K(ATP) channel function. This workload was sufficient to induce K(ATP) channel opening, resulting in membrane hyperpolarization as well as reduction in action potential overshoot and duration. Loss of K(ATP) channel function resulted in increased calcium release and aggravated activity-induced heat production. Thus, this study identifies low-intensity workload as a trigger for opening skeletal muscle K(ATP) channels and establishes that this coupling is important for regulation of myocyte function and thermogenesis. These mechanisms may provide a foundation for novel strategies to combat metabolic derangements when energy conservation or dissipation is required.