BPS2024 Full Program & Abstracts

11:30 am – 1:00 pm Nanion Technologies High Fidelity Electrophysiology: From Single Channels to High Throughput and Transporters In-Between Speaker: Tim Strassmaier, Director of Scientific Operations, Nanion Technologies Inc For over 20 years, Nanion Technologies has been providing diverse solutions for electrophysiologists worldwide. We aim to successfully implement innovative technologies in the fields of ion channel auto mated patch clamp (APC) electrophysiology, monitoring of cell viabil ity and contraction, as well as electrogenic transporters, with various throughput capabilities. This year, our symposium will start with an introduction by Dr. Tim Strassmaier (Director of Scientific Operations, Nanion Technologies Inc.) who will guide you through the overall capabilities of Nanion´s portfolio. Following this, we will welcome our speakers, whose work focuses on ion channel and transporter physi ology and pathophysiology. Structural Investigation of Ryanodine Receptor - Small Molecule Interactions Speaker: Filip Van Petegem, Professor Biochemistry and Molecular Biology, The University of British Columbia Dr. Filip Van Petegem will present cryo-electron microscopy and planar lipid bilayer electrophysiology on Ryanodine Receptors (RyRs), large calcium release channels located in the membranes of the ER and SR. These channels are targets for tens of proteins and small molecules that can alter their gating, and are involved in a wide range of channelopathies including malignant hyperthermia, CPVT, and central core disease. An overview will be presented on the vari ous molecules for which structural information is now available. This includes calcins, small peptides produced by scorpions. These can cross the plasma membrane, produce subconductance states and create asymmetry in the RyRs. Ion Channel Targeted Small Molecule and Antibody Therapeutic Programs Speaker: Franck Potet, Director, Electrophysiology, OmniAb Inc Ion channels are important therapeutic targets for many disease states and high throughput automated patch clamp is a useful tool to record ion channel activity in cell lines, stem cells and primary cells. The ability to investigate the effects of small molecules and large antibody compounds at high throughput is crucial for efficient drug discovery. At Icagen, the SyncroPatch 384 is used in multiple pro grams for drug discovery, some of which will be described in this talk. Functional Characterization of Human GAT1 Through Solid Sup ported Membrane-Based Electrophysiology Speaker: Rocco Zerlotti, Application Scientist, Nanion Technologies GmbH Dysregulation in GABA transport has been linked to many neurologi cal disorders, hence hGAT1 is an important target for their medi cal treatment. It is important to have tools to measure the GABA transporter, which can be achieved using solid supported membrane (SSM) electrophysiology. At the synapse, GAT1 exploits the Na+ gra dient to energize the uphill re-uptake of GABA from the synaptic cleft into the presynaptic neuron. Samples prepared from CHO cells stably expressing GAT1 were used the SURFE2R N1, and GABA-induced currents were elicited using the substrate-containing activating buf fer. Three different electrogenic events were detected, two faster components and a slower component corresponding to the transport event. The SURFE2R technology is a useful tool to study GAT1 as well as other transporters, membrane pumps and leak channels.

we show that a modulator enhances the binding of targeted splice sites by changing the off-, but not on-, rates. The magnitude of the changes in binding kinetics in vitro mirror those measured in vivo for changes in mRNA isoform generation, suggesting that U1 lifetime could be at least partially limiting for splicing in cells. Our results demonstrate the power of single molecule fluorescence for revealing complex RNA pharmacol ogy. PIP2 Is a Negative Regulator of NaV1.4 Channels Gating Speaker: Kirin Gada, Jordie Kamuene & Leigh Plant, Department of Pharmaceutical Sciences and the Center for Drug Discovery, Northeastern University Voltage-gated sodium (NaV) channels activate in response to depolar ization, causing the rapid influx of Na+ ions that initiates action poten tials in excitable cells. NaV channel gating is tightly controlled, with perturbations leading to a range of diseases. Recently, we reported that the ubiquitous signaling phospholipid, PI(4,5)P2 is a negative regu lator of NaV1.4 channels gating. Combining patch-clamp with opto genetic activation of specific, membrane associated phosphoinositide phosphatases we showed that dephosphorylating PI(4,5)P2 left-shifts the voltage-dependence of NaV1.4 channels to more hyperpolarized potentials, slows the rate of fast inactivation, augments the persistent late current, and speeds recovery from fast inactivation. Using TIRF microscopy, we show that the changes to NaV1.4 gating coincide with decoupling of a fluorescent PI(4,5)P2-biosensor from the plasma mem brane. About Mad City Labs Mad City Labs designs and manufactures a complete product line of high-precision piezo nanopositioners, micropositioners, AFM, and Single Molecule Microscopes. Visit www.madcitylabs.com or stop by Booth #700 during the meeting! Room 103C: Monday, February 12 9:30 am – 11:00 am Sophion Bioscience A/S Recent Advances in Automated Patch Clamp Assays Using Primary and iPSC-Derived Cells; and Virtual Screening for Modulators of KCa, Nav1.7, and GABA-A Channels: Does it Work? Successful ion channel drug discovery requires the integration of mul tiple technologies and workflows. Sophion Bioscience is a leader in automated patch clamp technology, providing low, medium and high throughput patch clamp systems to the drug discovery industry and academia. The QPatch and Qube are fully automated patch clamp systems, executing simultaneous 16, 48 or 384 parallel patch clamp recordings in conjunction with computer controlled liquid handling and on-board cell handling. The QPatch Compact is a manual patch clamp system that can execute individual or simultaneous 8 patch clamp recordings. Sophion provides customers with robust, ion channel and electrophysiological workflows for the drug development of ion chan nel targets. During this workshop, speakers will provide insight into the use of these systems with primary and iPSC cells, and the use of virtual screening in comparison to automated patch clamp in the drug discov ery process. Speakers Daniel Sauter, Scientific Sales Manager, Sophion Bioscience A/S Heike Wulff, Professor, University of California, Davis

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