Why attend?

Join us to learn how Automated Patch Clamp (APC) is advancing research in channelopathies and lysosomal ion channels, through real cases studies from SyncroPatch 384 grant recipients from 2023.

Talk abstracts

• Evaluating channelopathies with high-throughput patch clamp

Speaker: Ivy Dick, University of Maryland

Voltage-gated Ca²⁺ channels (VGCCs) are critical for the normal function of excitable cells. Genetic mutations in these channels lead to various disorders affecting the heart and brain. Among them, Ca_V1.2 mutations are associated with Timothy syndrome (TS)which presents with long QT syndrome (LQTS), cardiac arrhythmia and neurodevelopmental delay or autism spectrum disorder.

While many Ca_V1.2 mutations are labelled as gain-of-function, the broad spectrum of patient symptoms suggests more complex underlying mechanisms. Instead, we propose that specific changes in channel biophysical properties underlie specific phenotypic outcomes:

• Impaired inactivation is closely linked to cardiac arrhythmia and LQTS.

• A leftward shift in voltage-dependent activation may be tied to neurodevelopmental symptoms in Ca_V1.2 channelopathies.

High-throughput automated patch clamp enables biophysical studies linking the functional effects of the growing number of mutations with patient phenotype, providing a critical tool for understanding the pathogenic mechanisms of channelopathies. Here, we show how this platform can be used to identify mutation-specific changes in Ca_V1.2 gating and link them to clinical phenotypes, providing a powerful approach to functionally characterize the expand the landscape of disease-associated ion channel variants.

• Enabling early drug discovery of lysosomal targets with the SyncroPatch 384

Speaker: Iwan Williams, Cardiff University

Following success with Nanion’s SP384 Research Grant, the Medicines Discovery Institute at Cardiff University has now integrated a permanent SyncroPatch 384 system into its workflow. The decision reflects the platform’s significant impact on early-stage drug discovery.

This presentation highlights how automated patch clamp has accelerated the team’s research on lysosomal ion channels, with particular focus on TMEM175, a lysosomal cation channel permeable to both potassium and protons. TMEM175 plays a central role in lysosomal pH regulation and is increasingly linked to the pathogenesis of Parkinson’s Disease.

Using SyncroPatch 384-based assays, has enabled to:

• Identify several promising activator and inhibitor chemical series through an ongoing structure–activity relationship campaign

• Develop tool compounds for characterizing TMEM175’s role in cellular homeostasis and disease