Abstract：
ATP-sensitive potassium (KATP) channels function as metabolic sensors that link cell membrane excitability to the cellular energy status by controlling potassium ion (K+) flow across the cell membrane according to intracellular ATP and ADP concentrations. As such, KATP channels influence a broad spectrum of physiological processes, including insulin secretion and cardiovascular functions. KATP channels are hetero-octamers, consisting of four inward rectifier potassium channel subunits, Kir6.1 or Kir6.2, and four sulfonylurea receptors (SURs), SUR1, SUR2A, or SUR2B. Different Kir6 and SUR isoforms assemble into KATP channel subtypes with distinct tissue distributions and physiological functions. Mutations in the genes encoding KATP channel subunits underlie various human diseases. Targeted treatment for these diseases requires subtype-specific KATP channel modulators. Rubidium ions (Rb+) also pass through KATP channels, and Rb+ efflux assays can be used to assess KATP channel function and activity. Flame atomic absorption spectroscopy (Flame-AAS) combined with microsampling can measure Rb+ in small volume, which provides an efficient tool to screen for compounds that alter KATP channel activity in Rb+ efflux assays. In this chapter, we describe a detailed protocol for Rb+ efflux assays designed to identify new KATP channel modulators with potential therapeutic utilities.
摘要：
ATP敏感性钾（KATP）通道作为代谢传感器，通过根据细胞内ATP和ADP浓度控制钾离子（K）流过细胞膜，将细胞膜兴奋性与细胞能量状态联系起来。因此，KATP通道影响广泛的生理过程，包括胰岛素分泌和心血管功能。KATP通道是异八聚体，由四个内向整流钾通道亚基组成，Kir6.1或Kir6.2，以及四种磺酰脲受体（SURs），SUR1,SUR2A,或SUR2B。不同的Kir6和SUR同工型组装成具有不同组织分布和生理功能的KATP通道亚型。编码KATP通道亚基的基因中的突变是各种人类疾病的基础。这些疾病的靶向治疗需要亚型特异性KATP通道调节剂。铷离子（Rb+）也通过KATP通道，和Rb+外排测定可用于评估KATP通道功能和活性。火焰原子吸收光谱法(Flame-AAS)结合微量采样可以小体积测量Rb+,这提供了在Rb+外排测定中筛选改变KATP通道活性的化合物的有效工具。在这一章中,我们描述了设计用于鉴定具有潜在治疗效用的新型KATP通道调节剂的Rb+外排测定的详细方案.
