kca3.1

No abstract text is available yet for this article.

No abstract text is available yet for this article.

BACKGROUD AND AIM: T lymphocytes are involved in the occurrence and development of essential hypertension, and potassium channels are thought to be critical for lymphocyte activation. This study is to examine the roles of the voltage-gated potassium channels (Kv1.3) and calcium-activated potassium channels (KCa3.1) in peripheral blood T lymphocytes in Kazakh hypertensive patients of Xinjiang, China, mainly focusing on the effects of these channels on nuclear factor of activated T cells (NFAT) and inflammatory cytokines of T lymphocytes...

The Ca2+ ion is used ubiquitously as an intracellular signaling molecule due to its high external and low internal concentration. Many Ca2+ -sensing ion channel proteins have evolved to receive and propagate Ca2+ signals. Among them are the Ca2+ -activated potassium channels, a large family of potassium channels activated by rises in cytosolic calcium in response to Ca2+ influx via Ca2+ -permeable channels that open during the action potential or Ca2+ release from the endoplasmic reticulum. The Ca2+ sensitivity of these channels allows internal Ca2+ to regulate the electrical activity of the cell membrane...

A novel peptide, Cm39, was identified in the venom of the scorpion Centruroides margaritatus . Its primary structure was determined. It consists of 37 amino acid residues with a MW of 3980.2 Da. The full chemical synthesis and proper folding of Cm39 was obtained. Based on amino acid sequence alignment with different K+ channel inhibitor scorpion toxin (KTx) families and phylogenetic analysis, Cm39 belongs to the α-KTx 4 family and was registered with the systematic number of α-KTx 4.8. Synthetic Cm39 inhibits the voltage-gated K+ channel hKV 1...

Ion channels play an important role for regulation of the exocrine and the endocrine pancreas. This review focuses on the Ca2+ -regulated K+ channel KCa 3.1, encoded by the KCNN4 gene, which is present in both parts of the pancreas. In the islets of Langerhans, KCa 3.1 channels are involved in the regulation of membrane potential oscillations characterizing nutrient-stimulated islet activity. Channel upregulation is induced by gluco- or lipotoxic conditions and might contribute to micro-inflammation and impaired insulin release in type 2 diabetes mellitus as well as to diabetes-associated renal and vascular complications...

Ion channels are non-conventional, druggable oncological targets. The intermediate-conductance calcium-dependent potassium channel (KCa 3.1) is highly expressed in the plasma membrane and in the inner mitochondrial membrane (mitoKCa 3.1) of various cancer cell lines. The role mitoKCa 3.1 plays in cancer cells is still undefined. Here we report the synthesis and characterization of two mitochondria-targeted novel derivatives of a high-affinity KCa 3.1 antagonist, TRAM-34, which retain the ability to block channel activity...

Mechanisms of synergistic agonist stimulation and modulation of the electrochemical driving force for anion secretion are still not fully explored in human pancreatic duct epithelial cells. The first objective of this study was therefore to test whether combined agonist stimulation augments anion transport responses in the Capan-1 monolayer model of human pancreatic duct epithelium. The second objective was to test the influence of H+ ,K+ -ATPase inhibition on anion transport in Capan-1 monolayers. The third objective was to analyze the expression and function of K+ channels in Capan-1, which could support anion secretion and cooperate with H+ ,K+ -ATPases in pH and potassium homeostasis...

The microenvironment of proliferative and aggressive tumours, such as the brain tumour glioblastoma multiforme (GBM), is often acidic, hypoxic, and nutrient deficient. Acid-sensing ion channels (ASICs) are proton-sensitive Na+ channels that have been proposed to play a role in pH sensing and in modulation of cancer cell migration. We previously reported that primary glioblastoma stem cells (GSCs), which grow as multicellular tumour spheroids, express functional ASIC1a and ASIC3, whereas ASIC2a is downregulated in GSCs...

Diffuse gliomas, particularly glioblastomas, are incurable brain tumours1 . They are characterized by networks of interconnected brain tumour cells that communicate via Ca2+ transients2-6 . However, the networks' architecture and communication strategy and how these influence tumour biology remain unknown. Here we describe how glioblastoma cell networks include a small, plastic population of highly active glioblastoma cells that display rhythmic Ca2+ oscillations and are particularly connected to others. Their autonomous periodic Ca2+ transients preceded Ca2+ transients of other network-connected cells, activating the frequency-dependent MAPK and NF-κB pathways...

Using cell-attached recordings from molecular layer interneurons (MLI) of the cerebellar cortex of adult mice expressing channel rhodopsin 2, we show that wide-field optical activation induces an increase in firing rate during illumination and a firing pause when the illumination ends (post-stimulation silencing; PSS). Significant spike rate changes with respect to basal firing rate were observed for optical activations lasting 200 ms and 1 s as well as for 1 s long trains of 10 ms pulses at 50 Hz. For all conditions, the net effect of optical activation on the integrated spike rate is significantly reduced because of PSS...

The Ca2+ activated K+ channel KCa3.1 is overexpressed in several human tumor cell lines, e.g. clear cell renal carcinoma, prostate cancer, non-small cell lung cancer. Highly aggressive cancer cells use this ion channel for key processes of the metastatic cascade such as migration, extravasation and invasion. Therefore, small molecules, which are able to image this KCa3.1 channel in vitro and in vivo represent valuable diagnostic and prognostic tool compounds. The [18F]fluoroethyltriazolyl substituted senicapoc was used as positron emission tomography (PET) tracer and showed promising properties for imaging of KCa3...

Peptide Lv is a small endogenous secretory peptide that is expressed in various tissues and conserved across different species. Patients with diabetic retinopathy, an ocular disease with pathological angiogenesis, have upregulated peptide Lv in their retinas. The pro-angiogenic activity of peptide Lv is in part through promoting vascular endothelial cell (EC) proliferation, migration, and sprouting, but its molecular mechanism is not completely understood. This study aimed to decipher how peptide Lv promotes EC-dependent angiogenesis by using patch-clamp electrophysiological recordings, Western immunoblotting, quantitative PCR, and cell proliferation assays in cultured ECs...

Rheumatoid arthritis (RA) is a common autoimmune disease characterized by chronic inflammation. Immune dysfunction is an essential mechanism in the pathogenesis of RA and directly linked to synovial inflammation and cartilage/bone destruction. Intermediate conductance Ca2+ -activated K+ channel (KCa3.1) is considered a significant regulator of proliferation, differentiation, and migration of immune cells by mediating Ca2+ signal transduction. Earlier studies have demonstrated abnormal activation of KCa3.1 in the peripheral blood and articular synovium of RA patients...

No abstract text is available yet for this article.

The calcium-activated potassium channel 3.1 (KCa 3.1) is overexpressed in many tumor entities and has predictive power concerning disease progression and outcome. Imaging of the KCa 3.1 channel in vivo using a radiotracer for positron emission tomography (PET) could therefore establish a potentially powerful diagnostic tool. Senicapoc shows high affinity and excellent selectivity toward the KCa 3.1 channel. We have successfully pursued the synthesis of the 18 F-labeled derivative [18 F]3 of senicapoc using the prosthetic group approach with 1-azido-2-[18 F]fluoroethane ([18 F]6) in a "click" reaction...

Lung cancer is one of the leading causes of cancer-related deaths worldwide. The Ca2+ -activated K+ channel KCa 3.1 contributes to the progression of non-small cell lung cancer (NSCLC). Recently, KCa 3.1 channels were found in the inner membrane of mitochondria in different cancer cells. Mitochondria are the main sources for the generation of reactive oxygen species (ROS) that affect the progression of cancer cells. Here, we combined Western blotting, immunofluorescence, and fluorescent live-cell imaging to investigate the expression and function of KCa 3...

Fluoride has been used in the internal recording solution for manual and automated patch clamp experiments for decades because it helps to improve the seal resistance and promotes longer lasting recordings. In manual patch clamp, fluoride has been used to record voltage-gated Na (NaV ) channels where seal resistance and access resistance are critical for good voltage control. In automated patch clamp, suction is applied from underneath the patch clamp chip to attract a cell to the hole and obtain a good seal...

We previously identified potentiators of KCa3.1 (DCEBIO) that stimulate Cl- secretion across HBEs expressing wild type (WT) CFTR. However, these compounds failed to stimulate Cl- secretion in F508del CFTR HBEs. Drug discovery efforts identified CFTR potentiators (VX-770) and correctors (VX-445, VX-661) for CF disease causing mutations, including F508del and G551D. Herein, we evaluated the effect of KCa3.1 potentiation on Cl- equivalent current (ICl ) across primary HBEs expressing WT, F508del and G551D CFTR...

The Ca2+ -activated SK4 K+ channel is gated by Ca2+ -calmodulin (CaM) and is expressed in immune cells, brain, and heart. A cryoelectron microscopy (cryo-EM) structure of the human SK4 K+ channel recently revealed four CaM molecules per channel tetramer, where the apo CaM C-lobe and the holo CaM N -lobe interact with the proximal carboxyl terminus and the linker S4-S5, respectively, to gate the channel. Here, we show that phosphatidylinositol 4-5 bisphosphate (PIP2) potently activates SK4 channels by docking to the boundary of the CaM-binding domain...