Lactic acid produced by anaerobic metabolism during cardiac ischemia is among several compounds suggested to trigger anginal chest pain; however, the pH reached when a coronary artery is occluded (pH 7.0 to 6.7) can also occur during systemic acidosis, which causes no chest pain. Here we show that lactate, acting through extracellular divalent ions, dramatically increases activity of an acid-sensing ion channel (ASIC) that is highly expressed on sensory neurons that innervate the heart. The effect should confer upon neurons that express ASICs an extra sensitivity to the lactic acidosis of local ischemia compared to acidity caused by systemic pathology.