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Biochim Biophys Acta Proteins Proteom 2021 Apr 19:140662. Epub 2021 Apr 19.

Department of Biology, Kocaeli University, Umuttepe, Kocaeli 41380, Turkey. Electronic address:

Scytalidium catalase is a homotetramer including heme d in each subunit. Its primary function is the dismutation of HO to water and oxygen, but it is also able to oxidase various small organic compounds including catechol and phenol. The crystal structure of Scytalidium catalase reveals the presence of three linked channels providing access to the exterior like other catalases reported so far. Read More

J Mol Biol 2021 Apr 19:166995. Epub 2021 Apr 19.

Cardiovascular Research Institute; Departments of Biochemistry and Biophysics, and Cellular and Molecular Pharmacology; California Institute for Quantitative Biomedical Research; Kavli Institute for Fundamental Neuroscience University of California, San Francisco, California 93858-2330 USA; Molecular Biophysics and Integrated Bio-imaging Division Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA. Electronic address:

Leak currents, defined as voltage and time independent flows of ions across cell membranes, are central to cellular electrical excitability control. The K (KCNK) potassium channel class comprises an ion channel family that produces potassium leak currents that oppose excitation and stabilize the resting membrane potential in cells in the brain, cardiovascular system, immune system, and sensory organs. Due to their widespread tissue distribution, Ks contribute to many physiological and pathophysiological processes including anesthesia, pain, arrythmias, ischemia, hypertension, migraine, intraocular pressure regulation, and lung injury responses. Read More

Biophys J 2021 Apr 19. Epub 2021 Apr 19.

Department of Biomedical Engineering, Northwestern University, Evanston, IL 60657, USA; Center for Synthetic Biology, Northwestern University, Evanston, IL 60657, USA. Electronic address:

Polyunsaturated fatty acids (PUFAs) modify the activity of a wide range of membrane proteins and are increasingly hypothesized to modulate protein activity by indirectly altering membrane physical properties. Among the various physical properties affected by PUFAs, the membrane area expansion modulus (K), which measures membrane strain in response to applied force, is expected to be a significant controller of channel activity. Yet the impact of PUFAs on membrane K has not been measured previously. Read More

Neuron 2021 Apr;109(8):1245-1247

Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA. Electronic address:

In this issue of Neuron, Xue et al. report high-resolution structures of the human cGMP-activated ion channel CNGA1 from rod photoreceptors. These structures provide valuable insights into the processes of cGMP-dependent activation and Ca block and permeation. Read More

J Phys Chem A 2021 Apr 22. Epub 2021 Apr 22.

Air Force Research Laboratory, Space Vehicles Directorate, Kirtland Air Force Base, Albuquerque, New Mexico 87117, United States.

We show how the powerful combination of temperature-dependent kinetics coupled with detailed statistical modeling can be used to derive dynamical information about transition state barrier heights, the importance of multiple entrance channel complexes, crossings between spin surfaces, energetics, product states, and other information for metal-ion reactions. The methods are not new, but with improved computers, ion sources, ion transport, and better detection techniques, the ability to derive such parameters from the combination of methods has improved greatly. Temperature-dependent kinetics is very sensitive to the above list of parameters because the energy is varied in a controlled way that can be easily modeled. Read More

J Chem Inf Model 2021 Apr 22. Epub 2021 Apr 22.

Groningen Institute for Biomolecular Sciences and Biotechnology, University of Groningen, 9747AG Groningen, The Netherlands.

The CorA family of proteins plays a housekeeping role in the homeostasis of divalent metal ions in many bacteria and archaea as well as in mitochondria of eukaryotes, rendering it an important target to study the mechanisms of divalent transport and regulation across different life domains. Despite numerous studies, the mechanistic details of the channel gating and the transport of the metal ions are still not entirely understood. Here, we use all-atom and coarse-grained molecular dynamics simulations combined with experiments to investigate the influence of divalent cations on the function of CorA. Read More

Br J Pharmacol 2021 Apr 22. Epub 2021 Apr 22.

National-Local Joint Engineering Research Center for Drug Research and Development (R&D) of Neurodegenerative Diseases, Dalian Medical University, No 9 Western Section, Lvshun South Road, Dalian City, P.R. China, 116044.

Background And Purpose: Microglia-related inflammation is associated with the pathology of Parkinson's disease (PD). Functional voltage-gated sodium channels (VGSCS) are involved in regulating microglial function. Here, we aim to investigate the effects of SVHRSP (scorpion venom heat-resistant synthesized peptide) on 6-OHDA-induced PD-like mouse model and reveal its underlying mechanism. Read More

Plant Physiol 2019 Jun;180(3):1322-1335

Plant Physiology, School of Biological Sciences, Washington State University, Pullman, Washington 99164-4236.

Photosynthesis is limited by the slow relaxation of nonphotochemical quenching, which primarily dissipates excess absorbed light energy as heat. Because the heat dissipation process is proportional to light-driven thylakoid lumen acidification, manipulating thylakoid ion and proton flux via transport proteins could improve photosynthesis. However, an important aspect of the current understanding of the thylakoid ion transportome is inaccurate. Read More

Am J Med Genet A 2021 Apr 21. Epub 2021 Apr 21.

Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.

Transient receptor potential channel C6 encoded by TRPC6 is involved in slit diaphragm formation in podocytes, and abnormalities of the TRPC6 protein cause various glomerular diseases. The first identified pathogenic variant of TRPC6 was found to cause steroid-resistant nephrotic syndrome that typically developed in adulthood and then slowly led to end-stage renal disease, along with a renal pathology of focal segmental glomerulosclerosis. Here, we report a patient with rapidly progressing infantile nephrotic syndrome and a heterozygous missense TRPC6 variant. Read More

Basic Res Cardiol 2021 Apr 21;116(1):28. Epub 2021 Apr 21.

Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, NE, 68198, USA.

Cardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Read More

Cell Mol Life Sci 2021 Apr 21. Epub 2021 Apr 21.

Laboratory of Endometrium, Endometriosis and Reproductive Medicine, Department of Development and Regeneration, KU Leuven, Herestraat 49, Box 611, 3000, Leuven, Belgium.

Transient receptor potential (TRP) channels play prominent roles in ion homeostasis by their ability to control cation influx. Mouse placentation is governed by the processes of trophoblast proliferation, invasion, differentiation, and fusion, all of which require calcium signaling. Although certain TRP channels have been shown to contribute to maternal-fetal transport of magnesium and calcium, a role for TRP channels in specific trophoblast functions has been disregarded. Read More

Biol Methods Protoc 2021 19;6(1):bpab003. Epub 2021 Mar 19.

Victor Chang Cardiac Research Institute, 405 Liverpool Street, Darlinghurst, New South Wales 2010, Australia.

is one of the 59 medically actionable genes recommended by the American College of Medical Genetics for reporting of incidental findings from clinical genomic sequencing. However, half of the reported variants in the ClinVar database are classified as variants of uncertain significance. In the absence of strong clinical phenotypes, there is a need for functional phenotyping to help decipher the significance of variants identified incidentally. Read More

Sci Rep 2021 Apr 21;11(1):8590. Epub 2021 Apr 21.

School of Basic Medicine, Gannan Medical University, Ganzhou, 341000, Jiangxi, China.

In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. Read More

Pflugers Arch 2021 Apr 21. Epub 2021 Apr 21.

Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Hibikino 2-4, Kitakyushu, 808-0196, Japan.

Action potentials play an important role in neurotransmitter release in response to taste. Here, I have investigated voltage-gated Na channels, a primary component of action potentials, in respective cell types of mouse fungiform taste bud cells (TBCs) with in situ whole-cell clamping and single-cell RT-PCR techniques. The cell types of TBCs electrophysiologically examined were determined immunohistochemically using the type III inositol 1,4,5-triphoshate receptor as a type II cell marker and synaptosomal-associated protein 25 as a type III cell marker. Read More

Cardiovasc Res 2021 Apr 21. Epub 2021 Apr 21.

Walter Brendel Centre of Experimental Medicine, Biomedical Center, Institute of Cardiovascular Physiology and Pathophysiology, Ludwig-Maximilians-Universität München, 82152, Planegg-Martinsried, Germany.

Aims: Neutrophil trafficking within the vasculature strongly relies on intracellular calcium signaling. Sustained Ca2+ influx into the cell requires a compensatory efflux of potassium to maintain membrane potential. Here, we aimed to investigate whether the voltage-gated potassium channel KV1. Read More

Cardiovasc Res 2021 Apr 21. Epub 2021 Apr 21.

Department of Medical Pharmacology and Physiology University of Missouri, Columbia, MO 65212, USA.

Aims: Cardiomyocyte Ca2+ homeostasis is altered with ageing and predisposes the heart to Ca2+ intolerance and arrhythmia. Transient Receptor Potential Vanilloid 4 (TRPV4) is an osmotically-activated cation channel with expression in cardiomyocytes of the aged heart. The objective of this study was to examine the role of TRPV4 in Ca2+ handling and arrhythmogenesis following ischaemia-reperfusion (I/R), a pathological scenario associated with osmotic stress. Read More

Handb Exp Pharmacol 2021 Apr 21. Epub 2021 Apr 21.

Department of Pharmaceutical Sciences, Northeastern University, Boston, MA, USA.

Two-pore domain potassium channels are formed by subunits that each contain two pore-loops moieties. Whether the channels are expressed in yeast or the human central nervous system, two subunits come together to form a single potassium selective pore. TOK1, the first two-domain channel was cloned from Saccharomyces cerevisiae in 1995 and soon thereafter, 15 distinct K subunits were identified in the human genome. Read More

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Robert M. Berne Cardiovascular Research Center, University of Virginia, Charlottesville, VA 22908;

Recent studies have focused on the contribution of capillary endothelial TRPV4 channels to pulmonary pathologies, including lung edema and lung injury. However, in pulmonary hypertension (PH), small pulmonary arteries are the focus of the pathology, and endothelial TRPV4 channels in this crucial anatomy remain unexplored in PH. Here, we provide evidence that TRPV4 channels in endothelial cell caveolae maintain a low pulmonary arterial pressure under normal conditions. Read More

Proc Natl Acad Sci U S A 2021 Apr;118(17)

Department of Nephrology, Charité-Universitätsmedizin Berlin, 10115 Berlin, Germany;

Gain-of-function mutations in the gene (encoding the T-type calcium channel Ca3.2) cause autosomal-dominant familial hyperaldosteronism type IV (FH-IV) and early-onset hypertension in humans. We used CRISPR/Cas9 to generate knockin mice as a model of the most common FH-IV mutation, along with corresponding knockout mice ( ). Read More

BMC Psychiatry 2021 Apr 20;21(1):201. Epub 2021 Apr 20.

Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, Singapore, 117599, Singapore.

Background: Functional near-infrared spectroscopy (fNIRS) is an emerging neuroimaging modality that provides a direct and quantitative assessment of cortical haemodynamic response during a cognitive task. It may be used to identify neurophysiological differences between psychiatric disorders with overlapping symptoms, such as bipolar disorder (BD) and borderline personality disorder (BPD). Hence, this preliminary study aimed to compare the cerebral haemodynamic function of healthy controls (HC), patients with BD and patients with BPD. Read More

Acta Trop 2021 Apr 17:105922. Epub 2021 Apr 17.

Department of Biotechnology, National Institute of Pharmaceutical Education and Research, SAS Nagar, Mohali160062, Punjab, India. Electronic address:

Visceral Leishmaniasis is a major neglected tropical disease with increasing incidences of drug resistance. This has led to the search for a suitable drug target for chemotherapeutic intervention. Potassium channels are a family of membrane proteins which play a vital role in homeostasis and any perturbation in them alters cell survival which makes them an attractive target. Read More

Cardiovasc Res 2021 Apr 20. Epub 2021 Apr 20.

Institute of Cardiovascular Research and Sport Medicine, German Sport University Cologne.

Eur Rev Med Pharmacol Sci 2021 Apr;25(7):3007-3014

Department of Neurology, Qingdao Hospital of Traditional Chinese Medicine (Qingdao Hiser Hospital), Qingdao, Shandong, China.

Objective: Cerebral hemorrhage can cause hemorrhagic stroke, leading to severe brain damage. MiRNA-155 is closely related to the development of stroke. However, the regulatory mechanism of miRNA-155 during cerebral ischemia has not yet been elucidated. Read More

Methods Mol Biol 2021 ;2302:137-151

Department of Biological Chemistry, University of California Los Angeles, Los Angeles, CA, USA.

Microcrystal electron diffraction (MicroED) enables atomic resolution structures to be determined from vanishingly small crystals. Soluble proteins typically grow crystals that are tens to hundreds of microns in size for X-ray crystallography. But membrane protein crystals often grow crystals that are too small for X-ray diffraction and yet too large for MicroED. Read More

Methods Mol Biol 2021 ;2302:49-67

Division of Pulmonology, Allergy/Immunology, Cystic Fibrosis, and Sleep, Department of Pediatrics, Emory + Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.

Ion channels play crucial roles in cell physiology, and are a major class of targets for clinically relevant pharmaceuticals. Because they carry ionic current, the function and pharmacology of ion channels can be studied using electrophysiological approaches that range in resolution from the single molecule to many millions of molecules. This chapter describes electrophysiological approaches for the study of one representative ion channel that is defective in a genetic disease, and that is the target of so-called highly effective modulator therapies now used in the clinic: the cystic fibrosis transmembrane conductance regulator (CFTR). Read More

Neurosci Bull 2021 Apr 20. Epub 2021 Apr 20.

Department of Anesthesiology, Duke University Medical Center, Durham, 27710, USA.

Programmed cell death protein 1 (PD-1) is an immune checkpoint modulator and a major target of immunotherapy as anti-PD-1 monoclonal antibodies have demonstrated remarkable efficacy in cancer treatment. Accumulating evidence suggests an important role of PD-1 in the central nervous system (CNS). PD-1 has been implicated in CNS disorders such as brain tumors, Alzheimer's disease, ischemic stroke, spinal cord injury, multiple sclerosis, cognitive function, and pain. Read More

Brain 2021 Apr 20. Epub 2021 Apr 20.

Institute of Neuroscience and Department of Neurology of the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

The unc-13 homolog B (UNC13B) gene encodes a presynaptic protein, mammalian uncoordinated 13-2 (Munc13-2), that is highly expressed in the brain-predominantly in the cerebral cortex-and plays an essential role in synaptic vesicle priming and fusion, potentially affecting neuronal excitability. However, the functional significance of UNC13B mutation in human disease is not known. In this study we screened for novel genetic variants in a cohort of 446 unrelated cases (families) with partial epilepsy without acquired causes by trio-based whole-exome sequencing. Read More

Elife 2021 Apr 20;10. Epub 2021 Apr 20.

Department of Cell Biology, Wuhan University, Wuhan, China.

The multimodal sensory channel transient receptor potential vanilloid-3 (TRPV3) is expressed in epidermal keratinocytes and implicated in chronic pruritus, allergy, and inflammation-related skin disorders. Gain-of-function mutations of TRPV3 cause hair growth disorders in mice and Olmsted Syndrome in human. We here report that mouse and human TRPV3 channel is targeted by the clinical medication dyclonine that exerts a potent inhibitory effect. Read More

J Physiol 2021 Apr 20. Epub 2021 Apr 20.

Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.

Key Points: Gap junctions formed by different connexins are expressed throughout the body and harbor unique channel properties that have not been fully defined mechanistically. Recent structural studies by Cryo-EM have produced high-resolution models of the related but functionally distinct lens connexins (Cx50 and Cx46) captured in a stable open state, opening the door for structure-function comparison. Here, we conducted comparative MD simulation and electrophysiology studies to dissect the isoform-specific differences in Cx46 and Cx50 intercellular channel function. Read More

Mol Genet Genomics 2021 Apr 19. Epub 2021 Apr 19.

Department of Pediatrics (Pediatric Critical Care, Pediatric Genomics Discovery Program), School of Medicine, Yale University, New Haven, CT, USA.

Next-generation sequencing platforms are being increasingly applied in clinical genetic settings for evaluation of families with suspected heritable disease. These platforms potentially improve the diagnostic yield beyond that of disease-specific targeted gene panels, but also increase the number of rare or novel genetic variants that may confound precise diagnostics. Here, we describe a functional testing approach used to interpret the results of whole exome sequencing (WES) in a family presenting with syncope and sudden death. Read More