Zuccolini Paolo, Gavazzo Paola, Pusch Michael
Institute of Biophysics, National Research Council, Genoa, Italy.
Front Pharmacol. 2022 May 24;13:906608. doi: 10.3389/fphar.2022.906608. eCollection 2022.
BK (KCa 1.1, Slo-1) is a K channel characterized by an allosteric regulation of the gating mechanism by Ca binding and voltage, and a high unitary conductance. The channel is expressed in many different tissues, where it is involved in the regulation or the fine-tuning of many physiological processes. Among other organs, BK is expressed in the pancreatic duct, a part of the gland important for the correct ionic composition of the pancreatic juice. Unfortunately, the pancreatic duct is also the site where one of the deadliest cancer types, the pancreatic duct adenocarcinoma (PDAC), develops. In the past years, it has been reported that continuous exposure of cancer cells to BK openers can have a significant impact on cell viability as well as on the ability to proliferate and migrate. Here, we first summarize the main BK channel properties and its roles in pancreatic duct physiology. Then we focus on the potential role of BK as a pharmacological target in PDAC. Moreover, we discuss how results obtained when employing BK activators on cancer cells can, in some cases, be misleading.
大电导钙激活钾通道(BK,KCa 1.1,Slo-1)是一种钾通道,其门控机制受钙结合和电压的变构调节,且单位电导较高。该通道在许多不同组织中表达,参与多种生理过程的调节或微调。在其他器官中,BK在胰腺导管中表达,胰腺导管是胰腺的一部分,对胰液的正确离子组成很重要。不幸的是,胰腺导管也是最致命的癌症类型之一——胰腺导管腺癌(PDAC)的发生部位。在过去几年中,有报道称癌细胞持续暴露于BK开放剂会对细胞活力以及增殖和迁移能力产生重大影响。在此,我们首先总结BK通道的主要特性及其在胰腺导管生理学中的作用。然后我们聚焦于BK作为PDAC药理靶点的潜在作用。此外,我们还讨论了在癌细胞上使用BK激活剂时获得的结果在某些情况下如何具有误导性。