Two-pore channels are ancient members of the voltage-gated ion channel superfamily that are expressed predominantly on acidic organelles such as endosomes and lysosomes. Here we review recent advances in understanding how TPCs are activated by their ligands and identify five salient features: (1) TPCs are Ca-permeable non-selective cation channels gated by NAADP. (2) NAADP activation is indirect through associated NAADP receptors. (3) TPCs are also Na-selective channels gated by PI(3,5)P. (4) PI(3,5)P activation is direct through a structurally-resolved binding site. (5) TPCs switch their ion selectivity in an agonist-dependent manner.
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http://dx.doi.org/10.1016/j.ceca.2022.102543 | DOI Listing |
Int J Mol Sci
December 2024
Department of Medical Biology, Amsterdam Cardiovascular Sciences, Amsterdam University Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Short QT syndrome type 3 (SQTS3 or SQT3), which is associated with life-threatening cardiac arrhythmias, is caused by heterozygous gain-of-function mutations in the gene. This gene encodes the pore-forming α-subunit of the ion channel that carries the cardiac inward rectifier potassium current (I). These gain-of-function mutations either increase the amplitude of I or attenuate its rectification.
View Article and Find Full Text PDFNat Chem
January 2025
Laboratory of Advanced Materials, Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, State Key Laboratory of Molecular Engineering of Polymers, Collaborative Innovation Center of Chemistry for Energy Materials (2011-iChEM), College of Chemistry and Materials, Fudan University, Shanghai, P. R. China.
The synthesis of mesoporous metal-organic frameworks (meso-MOFs) is desirable as these materials can be used in various applications. However, owing to the imbalance in structural tension at the micro-scale (MOF crystallization) and the meso-scales (assembly of micelles with MOF subunits), the formation of single-crystal meso-MOFs is challenging. Here we report the preparation of uniform single-crystal meso-MOF nanoparticles with ordered mesopore channels in microporous frameworks with definite arrangements, through a cooperative assembly method co-mediated by strong and weak acids.
View Article and Find Full Text PDFACS Omega
December 2024
School of Safety Engineering, China University of Mining and Technology, Xuzhou 221116, Jiangsu, China.
Hot dry rock (HDR) is a novel green, low-carbon energy. Its development requires the creation of fracture channels in deep thermal reservoirs. Traditional methods such as hydraulic fracturing have limited effectiveness in reservoir stimulation, so a method of liquid nitrogen cold shock was proposed.
View Article and Find Full Text PDFPLoS One
December 2024
Laboratory of Biomolecular Research, Paul Scherrer Institute, Villigen, Switzerland.
Gap junction intercellular communication (GJIC) between two adjacent cells involves direct exchange of cytosolic ions and small molecules via connexin gap junction channels (GJCs). Connexin GJCs have emerged as drug targets, with small molecule connexin inhibitors considered a viable therapeutic strategy in several diseases. The molecular mechanisms of GJC inhibition by known small molecule connexin inhibitors remain unknown, preventing the development of more potent and connexin-specific therapeutics.
View Article and Find Full Text PDFSci Rep
December 2024
Department of Respiratory Medicine, Hunan Provincial People's Hospital (The First-Affiliated Hospital of Hunan Normal University), No. 61 Jiefang Xi Road, Changsha, Hunan, 410219, China.
Pulmonary arterial hypertension (PAH) is a serious medical condition that causes a failure in the right heart. Two-pore channel 2 (TPC2) is upregulated in PAH, but its roles in PAH remain largely unknown. Our investigation aims at the mechanisms by which TPC2 regulates PAH development.
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