Novel Fluorescence-Based High-Throughput FLIPR Assay Utilizing Membrane-Tethered Genetic Calcium Sensors to Identify T-Type Calcium Channel Modulators.

ABSTRACT: T-type voltage-gated Ca²⁺ channels have been implicated in many human disorders, and there has been increasing interest in developing highly selective and potent T-type Ca²⁺ channel modulators for potential clinical use. However, the unique biophysical properties of T-type Ca²⁺ channels are not conducive for developing high-throughput screening (HTS) assays to identify modulators, particularly potentiators. To illustrate, T-type Ca²⁺ channels are largely inactivated and unable to open to allow Ca²⁺ influx at -25 mV, the typical resting membrane potential of the cell lines commonly used in cellular screening assays. To address this issue, we developed cell lines that express K_ir2.3 channels to hyperpolarize the membrane poten

SUBMITTER: Zhang YL 

PROVIDER: S-EPMC8923061 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature