In vivo and in vitro phosphorylation of the T lymphocyte type n (Kv1.3) potassium channel.

BACKGROUND: Potassium channels, encoded by more than seventy genes, are cell excitability transmembrane proteins and become evident to play essential roles in tumor biology. OBJECTIVE: The deregulation of potassium channel genes has been related to cancer development and patient prognosis. The objective of this study is to understand the role of potassium channels in lung cancer. METHODS: We examined all potassium channel genes and identified that KCNN4 is the most significantly overexpressed one in lung adenocarcinoma. The role and mechanism of KCNN4 in lung adenocarcinoma were further investigated by in vitro cell and molecular assay and in vivo mouse xenograft models. RESULTS: We revealed that the silencing of KCNN4 significantly inhibits cell proliferation, migration, invasion, and tumorigenicity of lung adenocarcinoma. Further studies showed that knockdown of KCNN4 promotes cell apoptosis, induces cell cycle arrested in the S phase, and is associated with the epithelial to mesenchymal transition (EMT) process. Most importantly, we demonstrated that KCNN4 regulates the progression of lung adenocarcinoma through P13K/AKT and MEK/ERK signaling pathways. The use of inhibitors that targeted AKT and ERK also significantly inhibit the proliferation and metastasis of lung adenocarcinoma cells. CONCLUSIONS: This study investigated the function and mechanism of KCNN4 in lung adenocarcinoma. On this basis, this means that KCNN4 can be used as a tumor marker for lung adenocarcinoma and is expected to become an important target for a potential drug.

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The Protective Effect of Protein Kinase C and Adenosine Triphosphate-Sensitive Potassium Channel Agonists Against Inflammation in Rat Endothelium and Vascular Smooth Muscle In Vitro and In Vivo

Anesthesia & Analgesia ◽

10.1213/01.ane.0000124679.86069.ad ◽

2004 ◽

pp. 556-561 ◽

Cited By ~ 4

Author(s):

Roman V. Plachinta ◽

Manuela J. M. de Klaver ◽

John K. Hayes ◽

George F. Rich

Keyword(s):

Smooth Muscle ◽

Protein Kinase C ◽

Protein Kinase ◽

Vascular Smooth Muscle ◽

Protective Effect ◽

Potassium Channel ◽

Adenosine Triphosphate ◽

Kinase C

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Experimental immunology Umbilical cord blood-derived dendritic cells loaded with BGC823 tumor antigens and DC-derived exosomes stimulate efficient cytotoxic T-lymphocyte responses and antitumor immunity in vitro and in vivo

Central European Journal of Immunology ◽

10.5114/ceji.2014.43713 ◽

2014 ◽

Vol 2 ◽

pp. 142-151 ◽

Cited By ~ 8

Author(s):

Shasha Guan ◽

Qianru Li ◽

Pingping Liu ◽

Xiaoyan Xuan ◽

Ying Du

Keyword(s):

Dendritic Cells ◽

T Lymphocyte ◽

Umbilical Cord Blood ◽

Antitumor Immunity ◽

Tumor Antigens ◽

Cytotoxic T Lymphocyte ◽

Lymphocyte Responses ◽

Experimental Immunology

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K+ channel blockade in the NTS alters efficacy of two cardiorespiratory reflexes in vivo

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.274.3.r677 ◽

1998 ◽

Vol 274 (3) ◽

pp. R677-R685 ◽

Cited By ~ 2

Author(s):

James W. Butcher ◽

Julian F. R. Paton

Keyword(s):

Potassium Channel ◽

Neuronal Excitability ◽

Baroreceptor Reflex ◽

Right Atrial ◽

K Channel ◽

Reflex Bradycardia ◽

Potassium Conductances ◽

Voltage Dependent

We investigated the role of potassium conductances in the nucleus of the solitary tract (NTS) in determining the efficacy of the baroreceptor and cardiopulmonary reflexes in anesthetized rats. The baroreceptor reflex was elicited with an intravenous injection of phenylephrine to evoke a reflex bradycardia, and the cardiopulmonary reflex was evoked with a right atrial injection of phenylbiguanide. Microinjection of two Ca-dependent potassium channel antagonists (apamin and charybdotoxin) into the NTS potentiated the baroreceptor reflex bradycardia. This may reflect the increased neuronal excitability observed previously in vitro with these blockers. In contrast, the Ca-dependent potassium channel antagonists attenuated the cardiopulmonary reflex, whereas voltage-dependent potassium channel antagonists (4-aminopyridine and dendrotoxin) attenuated both the baro- and cardiopulmonary reflexes when microinjected into the NTS. The possibility that the reflex attenuation observed indicates a predominant distribution of certain potassium channels on γ-aminobutyric acid interneurons is discussed.

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A causal role for TRESK loss of function in migraine mechanisms

Brain ◽

10.1093/brain/awz342 ◽

2019 ◽

Vol 142 (12) ◽

pp. 3852-3867 ◽

Cited By ~ 12

Author(s):

Philippa Pettingill ◽

Greg A Weir ◽

Tina Wei ◽

Yukyee Wu ◽

Grace Flower ◽

...

Keyword(s):

Potassium Channel ◽

Drug Target ◽

Causal Role ◽

Potential Drug Target ◽

Potential Drug ◽

Loss Of Function

The two-pore potassium channel TRESK is a potential drug target in pain and migraine. Pettingill et al. show that the F139WfsX2 mutation causes TRESK loss of function and hyperexcitability in nociceptors derived from iPSCs of patients with migraine. Cloxyquin, a TRESK activator, reverses migraine-relevant phenotypes in vitro and in vivo.

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Galanin Inhibits Gut-Related Vagal Neurons in Rats

Journal of Neurophysiology ◽

10.1152/jn.00869.2003 ◽

2004 ◽

Vol 91 (5) ◽

pp. 2330-2343 ◽

Cited By ~ 11

Author(s):

Zhenjun Tan ◽

Ronald Fogel ◽

Chunhui Jiang ◽

Xueguo Zhang

Keyword(s):

Potassium Channel ◽

Reversal Potential ◽

Outward Current ◽

Motor Nucleus ◽

Dorsal Vagal Complex ◽

Solitary Tract ◽

Membrane Hyperpolarization ◽

Dorsal Motor Nucleus

Galanin plays an important role in the regulation of food intake, energy balance, and body weight. Many galanin-positive fibers as well as galanin-positive neurons were seen in the dorsal vagal complex, suggesting that galanin produces its effects by actions involving vagal neurons. In the present experiment, we used tract-tracing and neurophysiological techniques to evaluate the origin of the galaninergic fibers and the effect of galanin on neurons in the dorsal vagal complex. Our results reveal that the nucleus of the solitary tract is the major source of the galanin terminals in the dorsal vagal complex. In vivo experiments demonstrated that galanin inhibited the majority of gut-related neurons in the dorsal motor nucleus of the vagus. In vitro experiments demonstrated that galanin inhibited the majority of stomach-projecting neurons in the dorsal motor nucleus of the vagus by suppressing spontaneous activity and/or producing a fully reversible dose-dependent membrane hyperpolarization and outward current. The galanin-induced hyperpolarization and outward current persisted after synaptic input was blocked, suggesting that galanin acts directly on receptors of neurons in the dorsal motor nucleus of the vagus. The reversal potential induced by galanin was close to the potassium ion potentials of the Nernst equation and was prevented by the potassium channel blocker tetraethylammonium, indicating that the inhibitory effect of galanin was mediated by a potassium channel. These results indicate that the dorsal motor nucleus of the vagus is inhibited by galanin derived predominantly from neurons in the nucleus of the solitary tract projecting to the dorsal motor nucleus of the vagus nerve. Galanin is one of the neurotransmitters involved in the vago-vagal reflex.

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MiRP3 acts as an accessory subunit with the BK potassium channel

AJP Renal Physiology ◽

10.1152/ajprenal.00598.2007 ◽

2008 ◽

Vol 295 (2) ◽

pp. F380-F387 ◽

Cited By ~ 12

Author(s):

Daniel I. Levy ◽

Sherry Wanderling ◽

Daniel Biemesderfer ◽

Steve A. N. Goldstein

Keyword(s):

Potassium Channel ◽

Mixed Complex ◽

Intercalated Cells ◽

Voltage Gated ◽

Calcium Dependent ◽

Culture Cells ◽

Urinary Potassium ◽

Α Subunits

MinK-related peptides (MiRPs) are single-span membrane proteins that assemble with specific voltage-gated K+ (Kv) channel α-subunits to establish gating kinetics, unitary conductance, expression level, and pharmacology of the mixed complex. MiRP3 (encoded by the KCNE4 gene) has been shown to alter the behavior of some Kv α-subunits in vitro but its natural partners and physiologic functions are unknown. Seeking in vivo partners for MiRP3, immunohistochemistry was used to localize its expression to a unique subcellular site, the apical membrane of renal intercalated cells, where one potassium channel type has been recorded, the calcium- and voltage-gated channel BK. Overlapping staining of these two proteins was found in rabbit intercalated cells, and MiRP3 and BK subunits expressed in tissue culture cells were found to form detergent-stable complexes. Electrophysiologic and biochemical evaluation showed MiRP3 to act on BK to reduce current density in two fashions: shifting the current-voltage relationship to more depolarized voltages in a calcium-dependent fashion (∼10 mV at normal intracellular calcium levels) and accelerating degradation of MiRP3-BK complexes. The findings suggest a role for MiRP3 modulation of BK-dependent urinary potassium excretion.

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