Planar patch clamp has revolutionized characterization of ion channel behavior in drug discovery primarily via advancement in high throughput. Lab use of planar technology, however, addresses different requirements and suffers from inflexibility to enable wide range of interrogation via a single cell. This work presents integration of planar patch clamp with microfluidics, achieving multiple solution exchanges for tailor-specific measurement and allowing rapid replacement of the cell-contacting aperture. Studies via endogenously expressed ion channels in HEK 293T cells were commenced to characterize the device. Results reveal the microfluidic concentration generator produces distinct solution/drug combination/concentrations on-demand. Volume-regulated chloride channel and voltage-gated potassium channels in HEK 293T cells immersed in generated solutions under various osmolarities or drug concentrations show unique channel signature under specific condition. Excitation and blockage of ion channels in a single cell was demonstrated via serial solution exchange. Robustness of the reversible bonding and ease of glass substrate replacement were proven via repeated usage of the integrated device. The present approach reveals the capability and flexibility of integrated microfluidic planar patch-clamp system for ion channel assays.
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http://dx.doi.org/10.1002/bit.23068 | DOI Listing |
J Integr Plant Biol
January 2025
College of Life Science and Technology, Hubei Hongshan Laboratory, Huazhong Agricultural University, Wuhan, 430070, China.
Hydrogen sulfide inhibits the inward-rectifying potassium ion current by inducing the persulfide modification on three cysteine residues of the inward potassium channel KAT1. This persulfidation inhibits the activity of KAT1 and KAT2 and suppresses the activity of heterologous channels formed by KAT1 and KAT2.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Institute of Chemistry Chinese Academy of Sciences, Key Laboratory of Organic Solids, Zhongguancun North First Street 2, 100190, 100190, Beijing, CHINA.
The regulation of oxidative stress in living cells is essential for maintaining cellular processes and signal transduction. However, developing straightforward strategies to activate oxidative stress-sensitive membrane channels in situ poses significant challenges. In this study, we presented a chemiluminescence resonance energy transfer (CRET) system based on a conjugated oligomer, oligo(p-phenylenevinylene)-imidazole (OPV-Im), designed for the activation of transient receptor potential melastatin 2 (TRPM2) calcium channels in situ by superoxide anion (O2•-) without requiring external light sources.
View Article and Find Full Text PDFBr J Pharmacol
January 2025
Institute of Neurophysiology, Uniklinik RWTH Aachen University, Aachen, Germany.
Background And Purpose: Phentolamine is a non-selective α-adrenoreceptor antagonist used to reverse local anaesthesia, for example, during dental procedures when a vasoconstrictor is co-applied. Phentolamine-mediated vasodilation leads to faster clearance of injected drugs. Previous electrophysiological studies hypothesized that phentolamine acts as a modulator of voltage-gated sodium channels, which could conflict with its indication as local anaesthetic reversal agent.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2025
Musculoskeletal Research Laboratory, Department of Orthopedics & Traumatology, The Chinese University of Hong Kong, Hong Kong, China.
Background: Regenerative capacity of skeletal muscles decreases with age. Deficiency in cystic fibrosis transmembrane conductance regulator (CFTR) is associated with skeletal muscle weakness as well as epithelial cell senescence. However, whether and how CFTR plays a role in skeletal muscle regeneration and aging were unclear.
View Article and Find Full Text PDFChemMedChem
January 2025
Universita degli Studi di Catania, Department of Drug Sciences, Viale A. Doria, 6, 95100, Catania, ITALY.
This study presents a series of tetrahydropyrrolo[3,4-c]pyrazole-based compounds designed as sigma-1 receptor (S1R) ligands, focusing on optimizing affinity and reducing off-target effects. We synthesized various derivatives from commercially available precursors and, through radioligand binding assays, assessed their binding affinity for S1R and sigma-2 receptor (S2R). Compound 19 (AD417), containing a benzyl group and an amide substituent, demonstrated notable S1R affinity (Ki = 75 nM) with 6-fold selectivity over S2R.
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