When cardiac（心脏的） or skeletal muscle is not receiving enough oxygen to meet metabolic¹（新陈代谢的） demands, a person will experience pain, such as angina（心绞痛） , chest pain during a heart attack, or leg pain during a vigorous sprint²（冲刺，短跑） . This type of pain is called "ischemic（缺血性的） " pain and is sensed in the body by receptors on sensory³ neurons. It has been suggested that lactic⁴ acid（乳酸） , which increases during muscle exertion⁵ under conditions where oxygen is low, is a potential mediator⁶ of ischemic pain via action at acid sensing channel #3 (ASIC3). However, the acid signal it generates is quite subtle and is unlikely to act alone. "In our study, we examined whether other compounds that appear during ischemia（局部缺血） might work synergistically with acid upon ASIC3," explains senior study author, Dr. Edwin W. McCleskey. "We found that another compound released from ischemic muscle, adenosine（腺苷） tri-phosphate (ATP), works together with acid by increasing the sensitivity of ASIC3 on sensory neurons." Importantly, ATP levels have been shown to rise rapidly outside ischemic muscle cells and synergistic（协同的） action of ATP and acid has been observed in animal models of ischemia.

The researchers went on to show that ATP binds⁷ to a membrane⁸ purine（嘌呤） receptor, called P2X, and that P2X and ASIC appear to form a molecular⁹ complex that serves to sensitize ASIC to acid. "Taken together, our results help to explain the paradox¹⁰（悖论，反论） that acid appears incapable¹¹ of triggering ischemic pain by itself yet buffering¹² acid severely¹³ decreases sensory detection of ischemic pain," concludes Dr. McCleskey. "ATP, which is released from oxygen-deprived contracting muscle, increases the ability of ASICs to respond to a slight decrease in pH."