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Tissue oxygen sensor function of NADPH oxidase isoforms, an unusual cytochrome aa3 and reactive oxygen species.

NADPH oxidase isoforms with different gp91phox subunits as well as an unusual cytochrome aa3 with a heme a/a3 relationship of 9:91 are discussed as putative oxygen sensor proteins influencing gene expression and ion channel conductivity. Reactive oxygen species (ROS) are important second messengers of the oxygen sensing signal cascade determining the stability of transcription factors or the gating of ion channels. The formation of ROS by a perinuclear Fenton reaction is imaged by 1 and 2 photon confocal microscopy revealing mitochondrial and non-mitochondrial generation.

The deletion of AQP4 and TRPV4 affects astrocyte swelling/volume recovery in response to ischemia-mimicking pathologies.

INTRODUCTION: Astrocytic Transient receptor potential vanilloid 4 (TRPV4) channels, together with Aquaporin 4 (AQP4), are suspected to be th … oyed single-cell RT-qPCR to assess the effect of TRPV4 and AQP4 deletion on the expression of other ion channels and transporters involved in the homeostatic functioning of astrocytes. RESULTS: Quantification of astrocyte volume changes during OGD revealed that the deletion of AQP4 reduces astrocyte swelling, while simultaneous deletion of both AQP4 and TRPV4 …

Fragile X Mental Retardation Protein Bidirectionally Controls Dendritic Ih in a Cell Type-Specific Manner between Mouse Hippocampus and Prefrontal Cortex.

Channelopathies are implicated in Fragile X syndrome (FXS), yet the dysfunction of a particular ion channel varies with cell type. We previo … ng upon the cellular milieu.SIGNIFICANCE STATEMENT Changes in dendritic function, and voltage-gated ion channels in particular, are increasingly the focus of neurological disorders. We, and others, previously identified cell type-specific channelopathies in a mouse of model of Fragile X syndrome. The present study shows that replacing Fragile X Mental Retardat …

Methamphetamine acutely inhibits voltage-gated calcium channels but chronically up-regulates L-type channels.

In neurons, calcium (Ca(2+) ) channels regulate a wide variety of functions ranging from synaptic transmission to gene expression. They also induce neuroplastic changes that alter gene expression following psychostimulant administration. Ca(2+) channel blockers have been considered as potential therapeutic agents for the treatment of methamphetamine (METH) dependence because of their ability to reduce drug craving among METH users. Here, we studied the effects of METH exposure on voltage-gated Ca(2+) channels using SH-SY5Y cells as a model of dopaminergic neurons. We found that METH has differ

ENaC contributes to macrophage dysfunction in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a chronic systemic disease caused by dysfunctional or absent cystic fibrosis transmembrane conductance regulator (CFTR). CFTR is expressed in human immune cells and plays a role in regulating innate immunity both directly and indirectly. Besides CFTR, research indicates that the epithelial sodium channel (ENaC) also contributes to dysfunction in CF airway epithelial cells. However, the impact of non-CFTR ion channel dysfunction on CF immune responses is not yet fully understood. A precise understanding of how CF immune function is regulated by ion channels m…

Indirectly gated Cl(-)-dependent Cl(-) channels sense physiological changes of extracellular chloride in the leech.

The maintenance of ion homeostasis requires adequate ion sensors. In leeches, 34 nephridial nerve cells (NNCs) monitor the Cl(-) concentration of the blood. After a blood meal, the Cl(-) concentration of leech blood triples and is gradually restored to its normal value within 48 h after feeding. As previously shown in voltage-clamp experiments, the Cl(-) sensitivity of the NNCs relies on a persistent depolarizing Cl(-) current that is turned off by an increase of the extracellular Cl(-) concentration. The activation of this Cl(-)-dependent Cl(-) current is independent of voltage and of extra-

Solution structure and proposed binding mechanism of a novel potassium channel toxin kappa-conotoxin PVIIA.

BACKGROUND: kappa-PVIIA is a 27-residue polypeptide isolated from the venom of Conus purpurascens and is the first member of a new class of conotoxins that block potassium channels. By comparison to other ion channels of eukaryotic cell membranes, voltage-sensitive potassium channels are relatively simple and methodology has been developed for mapping their interactions with small-peptide toxins. PVIIA, therefore, is a valuable new probe of potassium channel structure. This study of the solution structure and mode of channel binding of PVIIA forms the basis for mapping the interacting residues…

Modulation of hNav by Tst1, a β-toxin purified from the scorpion Tityus stigmurus.

Scorpion venoms are known as a rich mixture of components, including peptides that can interact with different ion channels, particularly voltage-gated potassium channels (Kv), calcium channels (Cav) and sodium channels (Nav), essential membrane proteins for various physiological functions in organisms. The present work aimed to characterize the modulation of hNa+-channels by Tst1, a peptide purified from the venom of Tityus stigmurus, using whole-cell patch clamp. Tst1 at 100 nM provoked current inhibition in Nav 1.3 (85.23%), Nav 1.2 (67.26%) and Nav 1.4 (63.43%), while Nav 1.1, 1.5, 1.6, an…

Bidirectional effects of hydrogen sulfide via ATP-sensitive K(+) channels and transient receptor potential A1 channels in RIN14B cells.

Hydrogen sulfide (H2S) reportedly acts as a gasotransmitter because it mediates various cellular responses through several ion channels including ATP-sensitive K(+) (KATP) channels and transient receptor potential (TRP) A1 channels. H2S can activate both KATP and TRPA1 channels at a similar concentration range. In a single cell expressing both channels, however, it remains unknown what happens when both channels are simultaneously activated by H2S. In this study, we examined the effects of H2S on RIN14B cells that express both KATP and TRPA1 channels. RIN14B cells showed several intracellular …

Effect of Lambert-Eaton myasthenic syndrome antibodies on autonomic neurons in the mouse.

Somatic muscle weakness and autonomic symptoms characterize the autoimmune Lambert-Eaton myasthenic syndrome (LEMS). The former results from IgG autoantibody-mediated down-regulation of P/Q-type voltage-gated calcium channels at motor nerve terminals and consequent reduction in acetylcholine release; the basis for the autonomic symptoms is unknown. Using omega-conotoxins GVIA and MVIIC and omega-agatoxin IVA that block N-, Q-, and P-type channels, we investigated ex vivo the calcium channels subserving transmitter release from postganglionic parasympathetic neurons in the bladder and from post

Broadening the clinical spectrum: molecular mechanisms and new phenotypes of ANO3-dystonia.

Anoctamin 3 (ANO3) belongs to a family of transmembrane proteins that form phospholipid scramblases and ion channels. A large number of ANO3 variants were identified as the cause of craniocervical dystonia, but the underlying pathogenic mechanisms remain obscure. It was suggested that ANO3 variants may dysregulate intracellular Ca2+ signalling, as variants in other Ca2+ regulating proteins like hippocalcin were also identified as a cause of dystonia. In this study, we conducted a comprehensive evaluation of the clinical, radiological and molecular characteristics of four individuals from four …

The Effects of Ca2+ on Membrane Potential with Altered Function of NALCN and K2P Channels.

Cells exhibit a membrane potential due to the differential distribution of ions and the density of channels, pumps, and exchangers. It is known in larval Drosophila that the membrane potential gravitates towards the equilibrium potential of K+ due to the high density of K2P channels. Higher extracellular Ca2+ ([Ca2+]o) tends to drive the resting membrane potential to a more negative state, while lowering it has an opposite effect. The expression of the K2P channel and NALCN was altered genetically to determine the sensitivity to changes in [Ca2+]o, and computational simulations using the theor

A polycystin-2 protein with modified channel properties leads to an increased diameter of renal tubules and to renal cysts.

Mutations in the PKD2 gene cause autosomal-dominant polycystic kidney disease but the physiological role of polycystin-2, the protein product of PKD2, remains elusive. Polycystin-2 belongs to the transient receptor potential (TRP) family of non-selective cation channels. To test the hypothesis that altered ion channel properties of polycystin-2 compromise its putative role in a control circuit controlling lumen formation of renal tubular structures, we generated a mouse model in which we exchanged the pore loop of polycystin-2 with that of the closely related cation channel polycystin-2L1 (enc…

Differential molecular information of maurotoxin peptide recognizing IK(Ca) and Kv1.2 channels explored by computational simulation.

BACKGROUND: Scorpion toxins are invaluable tools for ion channel research and are potential drugs for human channelopathies. However, it is still an open task to determine the molecular basis underlying the diverse interactions between toxin peptides and ion channels. The inhibitory peptide Maurotoxin (MTX) recognized the distantly related IK(Ca) and Kv1.2 channel with approximately the same potency and using the same functional residues, their differential binding mechanism remain elusive. In this study, we applied computational methods to explore the differential binding modes of MTX to Kv1.…

[Interaction of the Latrodectus tredecimguttatus spider venom with liposomes].

It is established that interaction of Latrodectus tredecimguttatus venom with bilayer phospholipid membranes of liposomes results in formation of ion channels. Liposome permeability variations are estimated by input and output of 86Rb+ and 45Ca2+ isotopes. It is shown that LaCl3 in 0.5 mM concentration decreases considerably both input and output of Rb+ in proteoliposomes and it may be used as an inhibitor of latrotoxin channels in experiments with phospholipid vesicles. When studying electrophoretic spectrum of proteins bound with liposomes it is shown that latrotoxin (a polypeptide) with mol…

Pain-associated Mediators and Axon Pathfinders in Fibromyalgia Skin Cells.

OBJECTIVE: To investigate whether the expression of cytokine, nociception-associated ion channel, and axon guidance genes in patients with s … l cultures. Gene expression of selected pro- and antiinflammatory cytokines, nociception-associated ion channels, and axon guidance cues was assessed with quantitative real-time PCR. RESULTS: In fibroblasts, transforming growth factor-ß1 (TGF-ß1) gene expression was higher in patients with FMS compared to controls (calf and thigh: p < 0.001). Also, expression …

Switchable Nanochannel Biosensor for H2S Detection Based on an Azide Reduction Reaction Controlled BSA Aggregation.

Hydrogen sulfide (H2S) is the third endogenous gaseous signal molecule in organisms that can directly increase the salt tolerance of plants … response rate, which will help us better understand the synergistic effect of H2S messengers in the ion channels of living organisms.

Targeting the two-pore channel 2 in cancer progression and metastasis.

The importance of Ca2+ signaling, and particularly Ca2+ channels, in key events of cancer cell function such as proliferation, metastasis, autophagy and angiogenesis, has recently begun to be appreciated. Of particular note are two-pore channels (TPCs), a group of recently identified Ca2+-channels, located within the endolysosomal system. TPC2 has recently emerged as an intracellular ion channel of significant pathophysiological relevance, specifically in cancer, and interest in its role as an anti-cancer drug target has begun to be explored. Herein, an overview of the cancer-related functions

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… While the name “TPC” suggests an ion channel with two separate pores, TPCs actually consist of two subunits forming a dimer. … TPC2 can also associate with the transient receptor potential mucolipin 1 (TRPML1) ion channel, but despite this interaction, TRPML1 and TPC2 function as independent ion channels [ 19 ]. …

Role of transient receptor potential channels in intestinal inflammation and visceral pain: novel targets in inflammatory bowel diseases.

Transient receptor potential (TRP) channels are a large group of ion channels that are prevalent in mammalian tissues. They are widely distributed in the central and peripheral nervous systems, and in nonneuronal cells, where they are implicated in sensing temperature, noxious substances, and pain. TRPs play an important role in immune response and nociception and, therefore, may be involved in the pathogenesis of inflammatory bowel diseases, whose major symptoms include chronic inflammatory state and abdominal pain. In this review, we summarize what is known on TRP channels in inflammatory bo…

Genetics and pathology of voltage-gated Ca2+ channels.

Neurotransmitter release, neuronal excitation, and a whole variety of other neuronal functions are controlled by the intra/extra cellular Ca2+ gradient. The major pathway for entry of Ca2+ into the excitable cells is mediated by voltage-gated Ca2+ channels. Several functional subclasses of voltage-dependent Ca2+ channels have been identified, based on their pharmacological, biophysical properties, and molecular cloning. Recently, three human diseases (familial hemiplegic migraine, episodic ataxia type 2, and spinocerebellar ataxia 6) were added to the growing list of ion-channel disorders, all