ABSTRACT

Transient Receptor Potential Melastatin 3 (TRPM3) is a Ca²⁺ permeable nonselective cation channel, activated by heat and chemical agonists, such as the endogenous neuro-steroid Pregnenolone Sulfate (PregS) and the chemical compound CIM0216. TRPM3 is expressed in peripheral sensory neurons of the dorsal root ganglia (DRG), and its role in noxious heat sensation in mice is well established. TRPM3 is also expressed in a number of other tissues, including the brain, but its role there has been largely unexplored. Recent reports showed that two mutations in TRPM3 are associated with a developmental and epileptic encephalopathy, pointing to an important role of TRPM3 in the human brain. Subsequent reports found that the two disease-associated mutations increased basal channel activity, and sensitivity of the channel to activation by heat and chemical agonists. This review will discuss these mutations in the context of human diseases caused by mutations in other TRP channels, and in the context of the biophysical properties and physiological functions of TRPM3.

摘要

瞬时受体电位 Melastatin 3 (TRPM3) 是一种 Ca ²⁺可渗透的非选择性阳离子通道，由热和化学激动剂激活，例如内源性神经类固醇孕烯醇酮硫酸盐 (PregS) 和化合物 CIM0216。TRPM3 在背根神经节 (DRG) 的外周感觉神经元中表达，其在小鼠有害热感中的作用已得到充分证实。TRPM3 也在许多其他组织中表达，包括大脑，但它在其中的作用在很大程度上尚未探索。最近的报告显示，TRPM3 的两个突变与发育性和癫痫性脑病有关，表明 TRPM3 在人脑中的重要作用。随后的报告发现，这两种疾病相关突变增加了基础通道活性，以及​​通道对热和化学激动剂激活的敏感性。