ASICs Function as Cardiac Lactic Acid Sensors During Myocardial Ischemia

From the point of view of sensation, the heart is a curious organ. Sensory neurons innervate it, but we all hope never to be aware of them. The only conscious sensation they cause is pain and the only trigger for this is ischemia—when the heart gets insufficient oxygen. It is a sensation often felt only in the last minute of life. This raises two fundamental questions: (1) what purpose do these neurons serve besides mediating ischemic pain?; (2) what signal activates them? Lactic acid is an obvious candidate for the signal because it is released by muscle whenever there is insufficient oxygen. However, researchers have argued that lactic acid cannot be a trigger for ischemic pain because metabolic acidosis does not cause chest pain even though it can drop pH to levels equivalent to those that occur during myocardial infarction. Here, we review data showing that cardiac sensory neurons express extremely high levels of an ion channel that is triggered by acid and is also enhanced by other chemicals that appear during ischemic acidosis, but not during metabolic acidosis. This resurrects consideration of lactic acid as a pain signal and provides a possible molecular target for selectively suppressing the signal.