Synaptic receptors for low pH in extracellular space:metabotropic receptors are an underestimated factor in stroke

In the brain,extracellular pH could decrease in certain diseases.Acidification,however,is especially attributable for stroke.Lactate accumulation in the absence of anaerobic respiration is the main,but not the only,reason for lowering pH in this condition(Wemmie et al.,2013).In addition,local pH changes in the synaptic cleft may result from the release of acidic content of synaptic vesicles(Sinning and Hubner,2013).Acidification is able to damage or even kill a neuron.The damaging effect of low pH can be mediated by a direct effect of protons on enzymes or transport systems.It can also,however,be mediated by specific receptors(Wemmie et al.,2013;Levin and Buck,2015).The most well studied class of pH receptors is ionotropic acid-sensing ion channels(ASIC).These are ion channels which are permeable for sodium and calcium.They open in response to extracellular acidification.Activation of these receptors could lead to neuronal death(Wemmie et al.,2013).ASIC-induced neuronal death is appeared to be involved in stroke-induced brain damage.This suggestion is supported by the fact that amiloride,which inhibits ASIC,has a neuroprotective effect in stroke(Xiong et al.,2004).