Why the study?
Chronic pain represents a large unmet clinical need, and Kv7.2/7.3 channels are promising therapeutic targets requiring medium throughput assays to identify and characterize modulators.
The study presents a novel medium throughput electrophysiological assay for identifying and characterizing Kv7.2/7.3 channel modulators, which are potential therapeutics for chronic pain.
Provides scalable tool for Kv7.2/7.3 modulator discovery; leaves open translation to chronic pain therapies.
Relief from chronic pain continues to represent a large unmet need. The voltage-gated potassium channel Kv7.2/7.3, also known as KCNQ2/3, is a key contributor to the control of resting membrane potential and excitability in nociceptive neurons and represents a promising target for potential therapeutics. In this study, we present a medium throughput electrophysiological assay for the identification and characterization of modulators of Kv7.2/7.3 channels, using the IonWorks Barracuda™ automated voltage clamp platform. The assay combines a family of voltage steps used to construct conductance curves with a unique analysis method. Kv7.2/7.3 modulators shift the activation voltage and/or change the maximal conductance of the current, and both parameters have been used to quantify compound mediated effects. Both effects are expected to modulate neuronal excitability in vivo. The analysis method described assigns a single potency value that combines changes in activation voltage and maximal conductance and is expected to predict compound mediated changes in excitability.
No takes yet. Share an insight, caveat, or question.
Wilenkin et al. (2019) studied this question.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: