Correlation of Optical and Automated Patch Clamp Electrophysiology for Identification of NaV1.7 Inhibitors.
SLAS Discov
; 25(5): 434-446, 2020 06.
Article
in En
| MEDLINE
| ID: mdl-32292096
ABSTRACT
The voltage-gated sodium channel Nav1.7 is a genetically validated target for pain; pharmacological blockers are promising as a new class of nonaddictive therapeutics. The search for Nav1.7 subtype selective inhibitors requires a reliable, scalable, and sensitive assay. Previously, we developed an all-optical electrophysiology (Optopatch) Spiking HEK platform to study activity-dependent modulation of Nav1.7 in a format compatible with high-throughput screening. In this study, we benchmarked the Optopatch Spiking HEK assay with an existing validated automated electrophysiology assay on the IonWorks Barracuda (IWB) platform. In a pilot screen of 3520 compounds, which included compound plates from a random library as well as compound plates enriched for Nav1.7 inhibitors, the Optopatch Spiking HEK assay identified 174 hits, of which 143 were confirmed by IWB. The Optopatch Spiking HEK assay maintained the high reliability afforded by traditional fluorescent assays and further demonstrated comparable sensitivity to IWB measurements. We speculate that the Optopatch assay could provide an affordable high-throughput screening platform to identify novel Nav1.7 subtype selective inhibitors with diverse mechanisms of action, if coupled with a multiwell parallel optogenetic recording instrument.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Patch-Clamp Techniques
/
High-Throughput Screening Assays
/
NAV1.7 Voltage-Gated Sodium Channel
/
Voltage-Gated Sodium Channel Blockers
Type of study:
Diagnostic_studies
Limits:
Animals
/
Humans
Language:
En
Journal:
SLAS Discov
Year:
2020
Document type:
Article
Affiliation country:
United States