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Updated: May 2, 2026

Ex Vivo Assessment of Contractility, Fatigability and Alternans in Isolated Skeletal Muscles
Published on: November 1, 2012
Interstitial ATP and norepinephrine concentrations in active muscle.
Jianhua Li1, Nicholas C King, Lawrence I Sinoway
1Division of Cardiology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, 500 University Dr, Hershey, PA 17033, USA. jzl10@psu.edu
Exercise increases sympathetic nervous system activity. In active muscle, elevated interstitial adenosine triphosphate (ATP) stimulates P2X receptors on sympathetic nerves, increasing norepinephrine (NE) release and maintaining blood pressure.
Area of Science:
- Physiology
- Neuroscience
- Biochemistry
Background:
- Sympathetic nervous system activity and norepinephrine (NE) are crucial for maintaining blood pressure during exercise.
- Contracting skeletal muscle releases adenosine triphosphate (ATP), and sympathetic nerves possess P2X receptors.
Purpose of the Study:
- To investigate if elevated interstitial ATP in skeletal muscle stimulates P2X receptors, thereby increasing interstitial NE concentrations.
- To test the hypothesis that ATP acts as a signaling molecule between contracting muscle and sympathetic nerves.
Main Methods:
- Microdialysis was used to collect interstitial fluid from rat skeletal muscle.
- High-performance liquid chromatography (HPLC) measured concentrations of ATP and NE.
- Experiments involved muscle stretch, intra-arterial ATP injection, and administration of P2X receptor antagonist (PPADS) and nucleotidase inhibitor (ARL67156).
Main Results:
- Muscle stretch significantly increased interstitial ATP ([ATP]i) and NE ([NE]i) levels.
- The increase in [NE]i was directly correlated with the rise in [ATP]i.
- ATP administration elevated [NE]i, an effect modulated by PPADS and ARL67156, confirming P2X receptor involvement.
Conclusions:
- Skeletal muscle releases ATP during contraction, which stimulates P2X receptors on sympathetic nerves.
- This ATP-mediated signaling increases interstitial NE concentrations, contributing to blood pressure regulation during exercise.
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