High Throughput Screening for Specific Inhibitors and Modulators of A Novel Potas

描述（由申请人提供）：最近发现的KCNH2 3.1钾通道是hERG1钾通道的一种脑选择性异构体，在精神分裂症患者的大脑中已被证明是增加的，这是精神分裂症出现的遗传危险因素，并影响神经元细胞活性和脑生理。由于许多现有的抗精神病药物与已知的Herg1通道结合，新亚型的发现为开发无心脏副作用的抗精神病药物提供了一个潜在的新靶点。该提案将使用现有的hERG通道高通量铊通量测定来筛选表达hERG通道新异构体的细胞系中通道调节活性的化合物。野生型hERG通道也将被平行筛选，以帮助确定KCNH2 3.1钾通道的选择性调节剂。所得化合物将在电生理学实验中得到验证。动物模型的可用性将允许未来在体内测试对与精神病相关的记忆和动物生理学其他方面的影响。

DESCRIPTION (provided by applicant): High Throughput Screening for Specific Inhibitors and Modulators of A Novel Potassium Channel KCNH2 3.1 Associated with Risk for Schizophrenia and its treatment Abstract A recently discovered KCNH2 3.1 potassium channel, a brain selective isoform of the hERG1 potassium channel, has been shown to be increased in the brains of patients with schizophrenia, a genetic risk factor for the emergence of schizophrenia and to affect neuronal cell activity and brain physiology. Because many available antipsychotic drugs bind to know Herg1 channels, the discovery of the novel isoform offers a potential new target for the development of antipsychotic drugs without cardiac side effects. This proposal will use the available Herg1 channel high throughput thallium flux assay to screen compounds for channel modulating activity in a cell line expressing the novel isoform of the hERG channel. The wild type hERG channel will also be screened in parallel to help define the selective modulators of this KCNH2 3.1 potassium channel. The resulting compounds will be validated in electrophysiology experiments. The availability of animal models will allow future testing in vivo for effects on memory and other aspects of animal physiology linked with psychosis.