scholarly journals Homeostasis Regulation by Potassium Channel Subfamily K Member 3 (KCNK3) in Various Fishes

2021 ◽  
Vol 8 ◽  
Author(s):  
Zheng-Yong Wen ◽  
Chuan-Jie Qin ◽  
Yun-Yun Lv ◽  
Yan-Ping Li ◽  
Yuan-Chao Zou ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Ion Homeostasis ◽  
Cell Volume Regulation ◽  
Metabolism Regulation ◽  
Potential Applications ◽  
Fatty Acids Metabolism ◽  
Homeostasis Regulation

Potassium channels are important for K+ transport and cell volume regulation, which play important roles in many biological processes such as hormone secretion, ion homeostasis, excitability, and cell development. In mammals, a total of 15 potassium channels were identified and they were divided into six subfamilies, including TALK (TALK1, TALK2, TASK2), TASK (TASK1, TASK3, TASK5), TREK (TREK1, TREK2, TRAAK), TWIK (TWIK1, TWIK2, KCNK7), THIK (THIK1, THIK2) and TRESK. TASK1, also known as potassium channel subfamily k member 3 (KCNK3), is the first member identified in the TASK subfamily. This K2P channel has potential applications in fish breeding and aquaculture industry due to its important roles in various physiological processes. Despite its functional role has been well studied in mammals; however, it is less known in fishes. In this review, we systematically summarize recent research advances of this critical potassium channel in representative fishes, such as gene number variation, tissue distribution, phylogeny, and potential homeostasis regulation role. This paper provides novel insights into the functional properties of these fish kcnk3 genes (including osmoregulation, energy homeostasis maintenance and fatty acids metabolism regulation), and also expands our knowledge about their variations among diverse fishes.

Medicinal Chemistry of Potassium Channel Modulators: An Update of Recent Progress (2011-2017)

2019 ◽  
Vol 26 (12) ◽  
pp. 2062-2084 ◽  
Author(s):  
Vivek K. Vyas ◽  
Palak Parikh ◽  
Jonali Ramani ◽  
Manjunath Ghate
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Small Molecule ◽  
Medicinal Chemistry ◽  
Hormone Secretion ◽  
K Channel ◽  
Biological Functions ◽  
Chemistry Research ◽  
Channel Inhibition ◽  
Potassium Channel Modulators

Background: Potassium (K+) channels participate in many physiological processes, cardiac function, cell proliferation, neuronal signaling, muscle contractility, immune function, hormone secretion, osmotic pressure, changes in gene expression, and are involved in critical biological functions, and in a variety of diseases. Potassium channels represent a large family of tetrameric membrane proteins. Potassium channels activation reduces excitability, whereas channel inhibition increases excitability. Objective: Small molecule K+ channel activators and inhibitors interact with voltage-gated, inward rectifying, and two-pore tandem potassium channels. Due to their involvement in biological functions, and in a variety of diseases, small molecules as potassium channel modulators have received great scientific attention. Methods: : In this review, we have compiled the literature, patents and patent applications (2011 to 2017) related to different chemical classes of potassium channel openers and blockers as therapeutic agents for the treatment of various diseases. Many different chemical classes of selective small molecule have emerged as potassium channel modulators over the past years. Conclusion: This review discussed the current understanding of medicinal chemistry research in the field of potassium channel modulators to update the key advances in this field.

scholarly journals Mitochondrial Dynamics and Microglia as New Targets in Metabolism Regulation

2020 ◽  
Vol 21 (10) ◽  
pp. 3450 ◽  
Author(s):  
Martina Chiurazzi ◽  
Martina Di Maro ◽  
Mauro Cozzolino ◽  
Antonio Colantuoni
Keyword(s):  
Energy Homeostasis ◽  
Mitochondrial Dynamics ◽  
Oxygen Species ◽  
Metabolism Regulation ◽  
Homeostasis Regulation ◽  
Agouti Related Protein ◽  
The Relationship ◽  
And Oxidative Stress ◽  
Cellular Organelles

Energy homeostasis regulation is essential for the maintenance of life. Neuronal hypothalamic populations are involved in the regulation of energy balance. In order play this role, they require energy: mitochondria, indeed, have a key role in ensuring a constant energy supply to neurons. Mitochondria are cellular organelles that are involved in dynamic processes; their dysfunction has been associated with many diseases, such as obesity and type 2 diabetes, indicating their importance in cellular metabolism and bioenergetics. Food intake excess can induce mitochondrial dysfunction with consequent production of reactive oxygen species (ROS) and oxidative stress. Several studies have shown the involvement of mitochondrial dynamics in the modulation of releasing agouti-related protein (AgRP) and proopiomelanocortin (POMC) neuronal activity, although the mechanisms are still unclear. However, recent studies have shown that changes in mitochondrial metabolism, such as in inflammation, can contribute also to the activation of the microglial system in several diseases, especially degenerative diseases. This review is aimed to summarize the link between mitochondrial dynamics and hypothalamic neurons in the regulation of glucose and energy homeostasis. Furthermore, we focus on the importance of microglia activation in the pathogenesis of many diseases, such as obesity, and on the relationship with mitochondrial dynamics, although this process is still largely unknown.

scholarly journals Remodeling of Arterial Tone Regulation in Postnatal Development: Focus on Smooth Muscle Cell Potassium Channels

2021 ◽  
Vol 22 (11) ◽  
pp. 5413
Author(s):  
Anastasia A. Shvetsova ◽  
Dina K. Gaynullina ◽  
Olga S. Tarasova ◽  
Rudolf Schubert
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Postnatal Development ◽  
Sympathetic Innervation ◽  
Treatment Strategies ◽  
Muscle Membrane ◽  
Postnatal Life ◽  
Vascular Control ◽  
Bkca Channels

Maturation of the cardiovascular system is associated with crucial structural and functional remodeling. Thickening of the arterial wall, maturation of the sympathetic innervation, and switching of the mechanisms of arterial contraction from calcium-independent to calcium-dependent occur during postnatal development. All these processes promote an almost doubling of blood pressure from the moment of birth to reaching adulthood. This review focuses on the developmental alterations of potassium channels functioning as key smooth muscle membrane potential determinants and, consequently, vascular tone regulators. We present evidence that the pattern of potassium channel contribution to vascular control changes from Kir2, Kv1, Kv7 and TASK-1 channels to BKCa channels with maturation. The differences in the contribution of potassium channels to vasomotor tone at different stages of postnatal life should be considered in treatment strategies of cardiovascular diseases associated with potassium channel malfunction.

KCNN4 promotes the progression of lung adenocarcinoma by activating the AKT and ERK signaling pathways

2021 ◽  
pp. 1-15
Author(s):  
Ping Xu ◽  
Xiao Mo ◽  
Ruixue Xia ◽  
Long Jiang ◽  
Chengfei Zhang ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Lung Adenocarcinoma ◽  
Potassium Channel ◽  
Signaling Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Tumor Biology ◽  
Erk Signaling ◽  
Mesenchymal Transition

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.

scholarly journals WIN55,212-2, a Dual Modulator of Cannabinoid Receptors and G Protein-Coupled Inward Rectifier Potassium Channels

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 484
Author(s):  
Dongchen An ◽  
Steve Peigneur ◽  
Jan Tytgat
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
G Protein ◽  
Cannabinoid Receptors ◽  
Inward Rectifier ◽  
Xenopus Laevis Oocyte ◽  
Inward Rectifier Potassium Channels ◽  
Wide Range ◽  
Cb2 Receptors ◽  
G Protein Coupled

The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. The present study established and validated the functional expression in a Xenopus laevis oocyte expression system of CB1 and CB2 receptors, interacting with heteromeric GIRK1/2 channels and a regulator of G protein signaling, RGS4. This ex vivo system enables the discovery of a wide range of ligands interacting orthosterically or allosterically with CB1 and/or CB2 receptors. WIN55,212-2, a non-selective agonist of CB1 and CB2, was used to explore the CB1- or CB2-GIRK1/2-RGS4 signaling cascade. We show that WIN55,212-2 activates CB1 and CB2 at low concentrations whereas at higher concentrations it exerts a direct block of GIRK1/2. This illustrates a dual modulatory function, a feature not described before, which helps to explain the adverse effects induced by WIN55,212-2 in vivo. When comparing the effects with other typical cannabinoids such as Δ9-THC, CBD, CP55,940, and rimonabant, only WIN55,212-2 can significantly block GIRK1/2. Interestingly, the inward rectifier potassium channel, IRK1, a non-G protein-coupled potassium channel important for setting the resting membrane voltage and highly similar to GIRK1 and GIRK2, is not sensitive to WIN55,212-2, Δ9-THC, CBD, CP55,940, or rimonabant. From this, it is concluded that WIN55,212-2 selectively blocks GIRK1/2.

Identification of domains that control the heteromeric assembly of Kir5.1/Kir4.0 potassium channels

2003 ◽  
Vol 284 (4) ◽  
pp. C910-C917 ◽  
Author(s):  
Angelos-Aristeidis Konstas ◽  
Christoph Korbmacher ◽  
Stephen J. Tucker
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Functional Diversity ◽  
Kir Channels ◽  
Selective Interaction ◽  
Inwardly Rectifying ◽  
In Cells ◽  
Heteromeric Channels

Heteromultimerization between different inwardly rectifying (Kir) potassium channel subunits is an important mechanism for the generation of functional diversity. However, little is known about the mechanisms that control this process and that prevent promiscuous interactions in cells that express many different Kir subunits. In this study, we have examined the heteromeric assembly of Kir5.1 with other Kir subunits and have shown that this subunit exhibits a highly selective interaction with members of the Kir4.0 subfamily and does not physically associate with other Kir subunits such as Kir1.1, Kir2.1, and Kir6.2. Furthermore, we have identified regions within the Kir4.1 subunit that appear to govern the specificity of this interaction. These results help us to understand the mechanisms that control Kir subunit recognition and assembly and how cells can express many different Kir channels while maintaining distinct subpopulations of homo- and heteromeric channels within the cell.

scholarly journals Activation-inactivation of potassium channels and development of the potassium-channel spike in internally perfused squid giant axons.

1981 ◽  
Vol 78 (1) ◽  
pp. 43-61 ◽  
Author(s):  
I Inoue
Keyword(s):  
Potassium Channels ◽  
Potassium Channel ◽  
Voltage Clamp ◽  
Time Constant ◽  
Equilibrium Potential ◽  
Giant Axons ◽  
Dependent Inactivation ◽  
Voltage Dependent ◽  
Time Courses ◽  
Calcium Permeability

A spike that is the result of calcium permeability through potassium channels was separated from the action potential is squid giant axons internally perfused with a 30 mM NaF solution and bathed in a 100 mM CaCl2 solution by blocking sodium channels with tetrodotoxin. Currents through potassium channels were studied under voltage clamp. The records showed a clear voltage-dependent inactivation of the currents. The inactivation was composed of at least two components; one relatively fast, having a time constant of 20--30 ms, and the other very slow, having a time constant of 5--10 s. Voltage clamp was carried out with a variety of salt compositions in both the internal and external solutions. A similar voltage-dependent inactivation, also composed of the two components, was recognized in all the current through potassium channels. Although the direction and intensity of current strongly depended on the salt composition of the solutions, the time-courses of these currents at corresponding voltages were very similar. These results strongly suggest that the inactivation of the currents in attributable to an essential, dynamic property of potassium channels themselves. Thus, the generation of a potassium-channel spike can be understood as an event that occurs when the equilibrium potential across the potassium channel becomes positive.

Cortisol – inspection in the physiology and stress

2018 ◽  
Vol 54 (1) ◽  
pp. 29-36
Author(s):  
Nikola Musiała ◽  
Iga Hołyńska-Iwan ◽  
Dorota Olszewska-Słonina
Keyword(s):  
Wide Spectrum ◽  
Hormone Secretion ◽  
Laboratory Diagnosis ◽  
The Body ◽  
Stress Hormone ◽  
Renal Handling ◽  
Peripheral Tissues ◽  
Neurotransmitter Secretion ◽  
Fatty Acids Metabolism ◽  
System Functioning

Cortisol, also called “the” stress hormone is a glucocorticoid secreted by the adrenal cortex. This hormone plays a significant role in maintaining homeostasis, according to the body’s total stress. Cortisol interferes with many organs, affects glucose and fatty acids metabolism and neurotransmitter secretion. Predominantly, cortisol influences the carbohydrate metabolism, stimulating gluconeogenesis in the liver and inhibiting glucose utilization in peripheral tissues. As it is an element “fight or flight” it also stimulates central nervous system and enhances blood flow. To some extent cortisol influences also the renal handling of electrolytes, namely: increasing sodium resorption, and renal excretion of potassium, calcium and phosphates. Through its anti-inflammatory and immunosuppressive character this glucocorticoid modulates the immune system functioning. Cortisol has a circadian rhythm following ACTH (adrenocorticotropic hormone) secretion. Increased cortisol levels are observed physiologically during stress and pathologically in Cushing’s syndrome. Chronic hypercortisolism is harmful or the body, and its effects present an extremely wide spectrum, including insulin resistance, obesity, insomnia and even depression. Thus, laboratory diagnosis of cortisol level is important for the diagnosis, monitoring and evaluate the effectiveness of hypercortisolism treatment.

scholarly journals Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control

Molecules ◽  
2018 ◽  
Vol 23 (12) ◽  
pp. 3071 ◽  
Author(s):  
Giustino Orlando ◽  
Sheila Leone ◽  
Claudio Ferrante ◽  
Annalisa Chiavaroli ◽  
Adriano Mollica ◽  
...  
Keyword(s):  
Gene Expression ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Reproductive Function ◽  
Inhibitory Effect ◽  
Bdnf Gene ◽  
Appetite Control ◽  
Hydroxyindoleacetic Acid ◽  
Puberty Onset

Besides its role as key regulator in gonadotropin releasing hormone secretion, reproductive function, and puberty onset, kisspeptin has been proposed to act as a bridge between energy homeostasis and reproduction. In the present study, to characterize the role of hypothalamic kisspeptin as metabolic regulator, we evaluated the effects of kisspeptin-10 on neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) gene expression and the extracellular dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIIA) concentrations in rat hypothalamic (Hypo-E22) cells. Our study showed that kisspeptin-10 in the concentration range 1 nM–10 μM was well tolerated by the Hypo-E22 cell line. Moreover, kisspeptin-10 (100 nM–10 μM) concentration independently increased the gene expression of NPY while BDNF was inhibited only at the concentration of 10 μM. Finally, kisspeptin-10 decreased 5-HT and DA, leaving unaffected NE levels. The inhibitory effect on DA and 5-HT is consistent with the increased peptide-induced DOPAC/DA and 5-HIIA/5-HT ratios. In conclusion, our current findings suggesting the increased NPY together with decreased BDNF and 5-HT activity following kisspeptin-10 would be consistent with a possible orexigenic effect induced by the peptide.

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