Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) hold the potential to revolutionize heart disease modeling and drug screening. However, capturing physiologically relevant action potentials (APs) has been challenging, particularly with conventional whole-cell (WC) patch-clamp methods. WC recordings often disrupt the cellular environment, leading to a reduction in AP duration due to the "washing out" of cytoplasmic components. By using perforated patch-clamp techniques, it is possible to maintain electrical access while preserving cellular integrity. Unlike WC, the perforated method creates small pores in the cell membrane using agents like nystatin, allowing ions to pass while retaining important cytoplasmic components. Applying this method has significantly improved AP recordings on the Sophion Qube 384 platform, demonstrating a success rate of up to 40%. For more details, please refer to the related links.

As summer comes to an end and the signs of autumn are felt, we bring you the quarterly overview from Sophion users. The third quarter has also been a very busy period for Sophion's platform in ion channel research. Many themes are covered, including Nav, Kv, Cav, ligand-dependent ion channels, neurological diseases, cancer, infectious diseases, safety pharmacology, as well as toxins and antitoxins, so you are sure to find something that catches your eye. From an excellent list of publications, we would like to highlight three particularly valuable and interesting developments. For more details, please see the related links.

Human induced pluripotent stem cells (hiPSCs) are a highly versatile platform for modeling human neurons, enabling the generation of excitatory neurons for in vitro models. To understand the electrophysiological properties of neurons, such as excitability and synaptic transmission, recording ion channels in hiPSC-derived neurons is key. Researchers can investigate not only healthy neurophysiological functions by capturing the dynamics of ion channel currents such as sodium, potassium, and calcium, but also dysfunctions related to neurological diseases such as epilepsy, autism, and neurodegenerative disorders. These models provide valuable tools for studying disease mechanisms and testing potential therapeutic interventions in patient-specific contexts. For more details, please see the related links.

The paper using QPatch Compact focuses on the study of the inhibition of the Nav1.8 ion channel by two new analgesic compounds, VX-150 and VX-548. The Nav1.8 channel is a major target in sensory neurons that detect pain and is extremely important for pain-related therapies. This research, conducted by a professor's laboratory at Harvard Medical School, utilized the QPatch Compact semi-automated patch clamp system to perform voltage clamp recordings and analyze the effects of these compounds on Nav1.8 sodium currents. For more details, please see the related links.

A PhD from the University of Copenhagen has made significant progress by using the Qube 384 automated patch clamp (APC) platform to record α5-containing GABAA receptors from acutely isolated primary neurons. This research highlights the importance of using natural primary hippocampal neurons to evaluate the effects of antipsychotic drugs on GABAergic activity, particularly from the perspective of drug discovery for cognitive function and schizophrenia. Previous studies have relied on heterologous expression systems, such as HEK cells expressing α5-containing GABAA receptors. However, this study emphasizes the value of investigating these effects in primary hippocampal neurons, which more accurately reflect physiological conditions. For more details, please see the related links.

One in three adults experiences chronic pain in their lives, and the effectiveness of treatment is limited, leading to a worsening opioid crisis. Understanding the balance between pain and chronic pain, as well as methods for pain treatment, is becoming increasingly important. Ion channels play a central role in both the physiological pain response and the pathophysiological changes underlying chronic pain. These specialized protein structures embedded in the cell membrane control the flow of ions such as sodium (Na+), potassium (K+), and calcium (Ca2+) across the cell membrane. The movement of these ions generates electrical signals that travel along neurons and ultimately reach the brain, where they are recognized as pain. For more details, please see the related links.

Our company is jointly developing a new protocol that enables efficient screening studies to identify modulators of Kv7.2/Kv7.3 channel activity using spider venom peptides. This will advance the understanding of gain-of-function mutations in channel-related epilepsy and potential therapies. For more details, please see the related links.

The Kv1.3 ion channel regulates the activation of T lymphocytes and controls membrane potential and calcium signaling in immune responses. Dysregulation is associated with autoimmune diseases such as multiple sclerosis, psoriasis, and rheumatoid arthritis. The Kv1.3 channel also plays a role in the proliferation and survival of cancer cells. Therefore, Kv1.3 channels are considered promising targets for the treatment of both autoimmune diseases and cancer. Efficient ion channel assays require consistent, robust, and functional membrane expression. Using a low-expressing Kv1.3 cell line, we classified cells based on Kv1.3 expression using the Tyto cell sorter (from Miltenyi Biotec), significantly improving the success rate of QPatch assays. For more details, please see the related links.

Kv7 ion channels, also known as KCNQ channels, play a crucial role in regulating neuronal excitability, smooth muscle tone, and cardiac action potentials. Dysfunction of Kv7.4 channels is associated with hearing loss, hypertension, and epilepsy, making them an important target for understanding and treating these conditions. This application report describes a highly successful Kv7.4 assay using our QPatch automated patch clamp platform. For more details, please refer to the related links.