Send to

Choose Destination
See comment in PubMed Commons below
Elife. 2016 May 24;5. pii: e15202. doi: 10.7554/eLife.15202.

Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels.

Author information

Departments of Chemistry and Chemical Biology and Physics, Harvard University, Cambridge, United States.
Howard Hughes Medical Institute, Harvard University, Cambridge, United States.


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.


biophysics; electrophysiology; high throughput screening; ion channels; neuroscience; none; optogenetics; structural biology

[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for eLife Sciences Publications, Ltd Icon for PubMed Central
    Loading ...
    Support Center