Fluorescence-Based Tl + −Influx Assays as a Novel Approach for Characterization of Small-Conductance Ca 2+ −Activated K + Channel Modulators

摘要: Small-conductance Ca(2+)-activated potassium (SK) channels constitute a family of ion that are regulated by the cytosolic Ca(2+) concentration. Increases in intracellular concentration ([Ca(2+)](i)) result opening channels, which turn will lead to changes membrane potential. As name implies, small conductance, but even so, they known play crucial role several physiological processes, such as modulation neurotransmitter and hormone secretion, well memory learning (e.g.,see Curr Med Chem 14:1437-1457, 2007). Owing central SK have attracted much attention potential drug targets, both with respect identification activators blockers channel activity for indications as, e.g., epilepsy, pain, urinary incontinence (see 2007; Pharm Des 12:397-406, 2006). Thus, great efforts been put into development robust high-throughput assays detection characterization modulators activity. In present chapter, we describe two fluorescence-based Tl(+)influx positive negative modulators.