Priest B T, Swensen A M, McManus O B
Department of Ion Channels, Merck Research Labs, Rahway, NJ 07065, USA.
Curr Pharm Des. 2007;13(23):2325-37. doi: 10.2174/138161207781368701.
Ion channels play essential roles in nervous system signaling, electrolyte transport, and muscle contraction. As such, ion channels are important therapeutic targets, and the search for compounds that modulate ion channels is accelerating. In order to identify and optimize ion channel modulators, assays are needed that are reliable and provide sufficient throughput for all stages of the drug discovery process. Electrophysiological assays offer the most direct and accurate characterization of channel activity and, by controlling membrane potential, can provide information about drug interactions with different conformational states. However, these assays are technically challenging and notoriously low-throughput. The recent development of several automated electrophysiology platforms has greatly increased the throughput of whole cell electrophysiological recordings, allowing them to play a more central role in ion channel drug discovery. While challenges remain, this new technology will facilitate the pharmaceutical development of ion channel modulators.
离子通道在神经系统信号传导、电解质转运和肌肉收缩中发挥着重要作用。因此，离子通道是重要的治疗靶点，寻找调节离子通道的化合物的研究正在加速。为了识别和优化离子通道调节剂，需要可靠且能为药物发现过程的各个阶段提供足够通量的检测方法。电生理检测提供了对通道活性最直接和准确的表征，并且通过控制膜电位，可以提供有关药物与不同构象状态相互作用的信息。然而，这些检测在技术上具有挑战性，并且通量极低。最近几种自动化电生理平台的开发极大地提高了全细胞膜片钳记录的通量，使其在离子通道药物发现中发挥更核心的作用。尽管挑战依然存在，但这项新技术将促进离子通道调节剂的药物研发。
