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10:00-11:00 Dr. Delphine Bichet / K2P Channels as Emerging Targets for Pain Treatment
Summary
Potassium channels are key regulators of cellular physiology. They establish the resting membrane potential, govern the repolarization of action potentials, and thus shape the excitability of neurons, muscle, and cardiac cells. Within this large family, K2P channels play a unique role providing a persistent K⁺ leak and responding to a variety of mechanical, thermal, and chemical stimuli. In this way, they serve as important modulators of cellular excitability and of the response to stimuli under both normal and pathological conditions.
During this seminar, I will present the evidence supporting the K2P channels in the regulation of nociceptive and painful stimuli, as well as their growing interest in therapeutic research in this field. After describing the expression of these channels in pain-related structures, I will discuss their involvement in regulating the excitability of neurons within these areas. I will then review experimental data obtained from various laboratories, including our own, and present preliminary results from our lab. Finally, we will explore pharmacological agents targeting these channels, examining their potential for pain modulation and their therapeutic promise for treating pain in humans.

11:00-12:00 Dr. Franck Chatelain / In silico structural profiling of hERG variants to classify arrhythmogenic risk
Summary
Inherited mutations in the KCNH2 gene, which encodes the cardiac hERG potassium channel, are to arrhythmogenic syndromes such as Long QT and Short QT syndromes. However, clinical interpretation of the growing number of missense variants - many of which are classified as variants of uncertain significance (VUS) - remains a pressing challenge. Here, we present a semi-automated in silico pipeline for predicting hERG variant pathogenicity, integrating five structural metrics – residue volume, hydrophobicity, charge, steric clashes, and proximity to pathogenic hotspots - into a composite score scaled to the ACMG classification system. Applied to a nationwide cohort of 358 French hERG variants, this framework identified 36 variants as likely pathogenic, of which a representative subset was functionally validated using high-throughput automated patch clamp. Functional phenotyping confirmed the structural predictions, including for several VUS, demonstrating that comprehensive structural scoring can reliably stratify variant pathogenicity. This approach offers a scalable, cost-effective pre-screening tool to guide clinical variant interpretation and prioritization for experimental validation.