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• W2017124821 abstract "Ischemic pain occurs when there is insufficient blood flow for the metabolic needs of an organ. The pain of a heart attack is the prototypical example. Multiple compounds released from ischemic muscle likely contribute to this pain by acting on sensory neurons that innervate muscle. One such compound is lactic acid. Here, we show that ASIC3 (acid-sensing ion channel #3) has the appropriate expression pattern and physical properties to be the detector of this lactic acid. In rats, it is expressed only in sensory neurons and then only on a minority (~40%) of these. Nevertheless, it is expressed at extremely high levels on virtually all dorsal root ganglion sensory neurons that innervate the heart. It is extraordinarily sensitive to protons (Hill slope 4, half-activating pH 6.7), allowing it to readily respond to the small changes in extracellular pH (from 7.4 to 7.0) that occur during muscle ischemia. Moreover, both extracellular lactate and extracellular ATP increase the sensitivity of ASIC3 to protons. This final property makes ASIC3 a coincidence detector of three molecules that appear during ischemia, thereby allowing it to better detect acidosis caused by ischemia than other forms of systemic acidosis such as hypercapnia." @default.
• W2017124821 created "2016-06-24" @default.
• W2017124821 creator A5031624167 @default.
• W2017124821 creator A5064389480 @default.
• W2017124821 date "2005-11-01" @default.
• W2017124821 modified "2023-10-18" @default.
• W2017124821 title "An acid-sensing ion channel that detects ischemic pain" @default.
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• W2017124821 doi "https://doi.org/10.1590/s0100-879x2005001100001" @default.
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