Methods for negating the impact of zinc contamination to allow characterization of positive allosteric modulators of glycine receptors.

ABSTRACT: Zinc is a ubiquitous contaminant in many buffers, purified products and common labware that has previously been suggested to impact on the results of functional GlyR studies and may inadvertently cause the effectiveness of some GlyR modulators to be over-estimated. This could greatly impact the assessment of potential drug-candidates and contribute to the reduced effectiveness of compounds that reach clinical stages. This is especially true for GlyR modulators being developed for pain therapeutics due to the changes in spinal zinc concentrations that have been observed during chronic pain conditions. In this study we use two-electrode voltage clamp electrophysiology to evaluate the metal chelators tricine and Ca-EDTA, and show that tricine produces inhibitory effects at GlyRα₁ t

SUBMITTER: Gallagher CI 

PROVIDER: S-EPMC11228362 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature