Meents Jannis E, Fischer Michael J M, McNaughton Peter A
Department of Pharmacology, University of Cambridge, Cambridge, United Kingdom.
Institute of Physiology, Uniklinik RWTH Aachen, Aachen, Germany.
PLoS One. 2017 Jan 11;12(1):e0170097. doi: 10.1371/journal.pone.0170097. eCollection 2017.
The TRPA1 ion channel is expressed in nociceptive (pain-sensitive) somatosensory neurons and is activated by a wide variety of chemical irritants, such as acrolein in smoke or isothiocyanates in mustard. Here, we investigate the enhancement of TRPA1 function caused by inflammatory mediators, which is thought to be important in lung conditions such as asthma and COPD. Protein kinase A is an important kinase acting downstream of inflammatory mediators to cause sensitization of TRPA1. By using site-directed mutagenesis, patch-clamp electrophysiology and calcium imaging we identify four amino acid residues, S86, S317, S428, and S972, as the principal targets of PKA-mediated phosphorylation and sensitization of TRPA1.
瞬时受体电位锚蛋白1（TRPA1）离子通道在伤害性（疼痛敏感）躯体感觉神经元中表达，并被多种化学刺激物激活，如烟雾中的丙烯醛或芥末中的异硫氰酸盐。在此，我们研究了炎症介质引起的TRPA1功能增强，这被认为在哮喘和慢性阻塞性肺疾病（COPD）等肺部疾病中很重要。蛋白激酶A是一种重要的激酶，作用于炎症介质下游，导致TRPA1致敏。通过使用定点诱变、膜片钳电生理学和钙成像技术，我们确定了四个氨基酸残基S86、S317、S428和S972，它们是蛋白激酶A介导的TRPA1磷酸化和致敏的主要靶点。
