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

DSpace/Manakin Repository

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

Citable link to this page

 

 
Title: Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels
Author: Zhang, Hongkang; Reichert, Elaine; Cohen, Adam E

Note: Order does not necessarily reflect citation order of authors.

Citation: Zhang, Hongkang, Elaine Reichert, and Adam E Cohen. 2016. “Optical electrophysiology for probing function and pharmacology of voltage-gated ion channels.” eLife 5 (1): e15202. doi:10.7554/eLife.15202. http://dx.doi.org/10.7554/eLife.15202.
Full Text & Related Files:
Abstract: 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. DOI: http://dx.doi.org/10.7554/eLife.15202.001
Published Version: doi:10.7554/eLife.15202
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907688/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:27662245
Downloads of this work:

Show full Dublin Core record

This item appears in the following Collection(s)

 
 

Search DASH


Advanced Search
 
 

Submitters