Mamet Julien, Baron Anne, Lazdunski Michel, Voilley Nicolas
Institut de Pharmacologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique-Unité Mixte de Recherche 6097, Sophia Antipolis, 06560 Valbonne, France.
J Neurosci. 2002 Dec 15;22(24):10662-70. doi: 10.1523/JNEUROSCI.22-24-10662.2002.
Tissue acidosis is an important feature of inflammation. It is a direct cause of pain and hyperalgesia. Protons activate sensory neurons mainly through acid-sensing ion channels (ASICs) and the subsequent membrane depolarization that leads to action potential generation. We had previously shown that ASIC transcript levels were increased in inflammatory conditions in vivo. We have now found that this increase is caused by the proinflammatory mediators NGF, serotonin, interleukin-1, and bradykinin. A mixture of these mediators increases ASIC-like current amplitude on sensory neurons as well as the number of ASIC-expressing neurons and leads to a higher sensory neuron excitability. An analysis of the promoter region of the ASIC3 encoding gene, an ASIC specifically expressed in sensory neurons and associated with chest pain that accompanies cardiac ischemia, reveals that gene transcription is controlled by NGF and serotonin.
组织酸中毒是炎症的一个重要特征。它是疼痛和痛觉过敏的直接原因。质子主要通过酸敏感离子通道（ASICs）激活感觉神经元，随后的膜去极化导致动作电位的产生。我们之前已经表明，在体内炎症条件下ASIC转录水平会升高。我们现在发现这种升高是由促炎介质神经生长因子（NGF）、血清素、白细胞介素-1和缓激肽引起的。这些介质的混合物会增加感觉神经元上ASIC样电流的幅度以及表达ASIC的神经元数量，并导致更高的感觉神经元兴奋性。对ASIC3编码基因启动子区域的分析表明，该基因转录受NGF和血清素的控制。ASIC3是一种在感觉神经元中特异性表达且与心脏缺血伴发的胸痛相关的ASIC。
