TY - JOUR TI - Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels AU - Zhang, Hongkang AU - Reichert, Elaine AU - Cohen, Adam E A2 - Raman, Indira M VL - 5 PY - 2016 DA - 2016/05/24 SP - e15202 C1 - eLife 2016;5:e15202 DO - 10.7554/eLife.15202 UR - https://doi.org/10.7554/eLife.15202 AB - Voltage-gated ion channels mediate electrical dynamics in excitable tissues and are an important class of drug targets. Channels can gate in sub-millisecond timescales, show complex manifolds of conformational states, and often show state-dependent pharmacology. Mechanistic studies of ion channels typically involve sophisticated voltage-clamp protocols applied through manual or automated electrophysiology. Here, we develop all-optical electrophysiology techniques to study activity-dependent modulation of ion channels, in a format compatible with high-throughput screening. Using optical electrophysiology, we recapitulate many voltage-clamp protocols and apply to Nav1.7, a channel implicated in pain. Optical measurements reveal that a sustained depolarization strongly potentiates the inhibitory effect of PF-04856264, a Nav1.7-specific blocker. In a pilot screen, we stratify a library of 320 FDA-approved compounds by binding mechanism and kinetics, and find close concordance with patch clamp measurements. Optical electrophysiology provides a favorable tradeoff between throughput and information content for studies of NaV channels, and possibly other voltage-gated channels. KW - optogenetics KW - electrophysiology KW - ion channels KW - high throughput screening JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -