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Identification 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 PDFBiological memory networks are thought to store information by experience-dependent changes in the synaptic connectivity between assemblies of neurons. Recent models suggest that these assemblies contain both excitatory and inhibitory neurons (E/I assemblies), resulting in co-tuning and precise balance of excitation and inhibition. To understand computational consequences of E/I assemblies under biologically realistic constraints we built a spiking network model based on experimental data from telencephalic area Dp of adult zebrafish, a precisely balanced recurrent network homologous to piriform cortex.
View Article and Find Full Text PDFFast Neuronal Calcium Signals in Brain Slices Loaded With Fluo-4 AM Ester.
Eur J Neurosci
January 2025
Université Grenoble Alpes, CNRS, LIPhy, Grenoble, France.
Staining brain slices with acetoxymethyl ester (AM) Ca dyes is a straightforward procedure to load multiple cells, and Fluo-4 is a commonly used high-affinity indicator due to its very large dynamic range. It has been shown that this dye preferentially stains glial cells, providing slow and large Ca transients, but it is questionable whether and at which temporal resolution it can also report Ca transients from neuronal cells. Here, by electrically stimulating mouse hippocampal slices, we resolved fast neuronal signals corresponding to 1%-3% maximal fluorescence changes.
View Article and Find Full Text PDFA Pharmacokinetic/Pharmacodynamic Study of Esomeprazole Comparing a Dual Delayed-Release Formulation (YYD601) to a Conventional Formulation Following Multiple Administrations in Healthy Adult Subjects.
Drug Des Devel Ther
January 2025
School of Medicine, Kyungpook National University and Department of Clinical Pharmacology and Therapeutics, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
Background: YYD601 is a new dual delayed-release formulation of esomeprazole, developed to enhance plasma exposure and prolong the duration of acid suppression.
Purpose: This study aimed to evaluate the safety, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of YYD601 20 mg following single and multiple oral administrations in healthy, fasting adult Koreans, and to compare these outcomes to those of the conventional esomeprazole 20 mg capsule.
Methods: A randomized, open-label, two-period crossover study was conducted in 28 participants, who were divided into two treatment groups: one group received YYD601 20 mg, and the other received conventional esomeprazole 20 mg, once daily for five consecutive days.
Opening of the cardiac voltage-gated Na+ channel (Nav1.5) is responsible for robust depolarization of the cardiac action potential, while inactivation, which rapidly follows, allows for repolarization. Regulation of both the voltage- and time-dependent kinetics of Nav1.
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