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Intelligent in-cell electrophysiology: Reconstructing intracellular action potentials using a physics-informed deep learning model trained on nanoelectrode array recordings.
Nat Commun
January 2025
Aiiso Yufeng Li Family Department of Chemical and Nano Engineering, University of California San Diego, La Jolla, CA, USA.
Intracellular electrophysiology is essential in neuroscience, cardiology, and pharmacology for studying cells' electrical properties. Traditional methods like patch-clamp are precise but low-throughput and invasive. Nanoelectrode Arrays (NEAs) offer a promising alternative by enabling simultaneous intracellular and extracellular action potential (iAP and eAP) recordings with high throughput.
View Article and Find Full Text PDFIdentification of Lauric Acid as a Potent Sodium Channel Na1.5 Blocker from Compound Chinese Medicine Wenxin Keli.
Drug Des Devel Ther
January 2025
State Key Laboratory of Component-Based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, 301617, People's Republic of China.
Purpose: The major cardiac voltage-gated sodium channel Na1.5 (I) is essential for cardiac action potential initiation and subsequent propagation. Compound Chinese medicine Wenxin Keli (WXKL) has been shown to suppress arrhythmias and heart failure.
View Article and Find Full Text PDFUltrafast multicellular calcium imaging of calcium spikes in mouse beta cells in tissue slices.
Acta Physiol (Oxf)
February 2025
Faculty of Medicine, University of Maribor, Maribor, Slovenia.
Background: The crucial steps in beta cell stimulus-secretion coupling upon stimulation with glucose are oscillatory changes in metabolism, membrane potential, intracellular calcium concentration, and exocytosis. The changes in membrane potential consist of bursts of spikes, with silent phases between them being dominated by membrane repolarization and absence of spikes. Assessing intra- and intercellular coupling at the multicellular level is possible with ever-increasing detail, but our current ability to simultaneously resolve spikes from many beta cells remains limited to double-impalement electrophysiological recordings.
View Article and Find Full Text PDFLongitudinal and Noninvasive Intracellular Recordings of Spontaneous Electrophysiological Activity in Rat Primary Neurons on Planar MEA Electrodes.
Adv Mater
January 2025
Italian Institute of Technology, Genoa, 16163, Italy.
Presently, the in vitro recording of intracellular neuronal signals on microelectrode arrays (MEAs) requires complex 3D nanostructures or invasive and approaches such as electroporation. Here, it is shown that laser poration enables intracellular coupling on planar electrodes without damaging neurons or altering their spontaneous electrophysiological activity, allowing the process to be repeated multiple times on the same cells. This capability distinguishes laser-based neuron poration from more invasive methods like electroporation, which typically serve as endpoint measurement for cells.
View Article and Find Full Text PDFA lever hypothesis for Synaptotagmin-1 action in neurotransmitter release.
Proc Natl Acad Sci U S A
January 2025
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390.
Neurotransmitter release is triggered in microseconds by Ca-binding to the Synaptotagmin-1 C-domains and by SNARE complexes that form four-helix bundles between synaptic vesicles and plasma membranes, but the coupling mechanism between Ca-sensing and membrane fusion is unknown. Release requires extension of SNARE helices into juxtamembrane linkers that precede transmembrane regions (linker zippering) and binding of the Synaptotagmin-1 CB domain to SNARE complexes through a "primary interface" comprising two regions (I and II). The Synaptotagmin-1 Ca-binding loops were believed to accelerate membrane fusion by inducing membrane curvature, perturbing lipid bilayers, or helping bridge the membranes, but SNARE complex binding through the primary interface orients the Ca-binding loops away from the fusion site, hindering these putative activities.
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