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The Journal of Physiology Apr 2017
Topics: Electrophysiological Phenomena; Heart; Humans; Potassium Channels
PubMed: 28370016
DOI: 10.1113/JP274181 -
International Journal of Molecular... Jan 2023Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of K+ ions through the biological membranes. According... (Review)
Review
Potassium channels are widely distributed integral proteins responsible for the effective and selective transport of K+ ions through the biological membranes. According to the existing structural and mechanistic differences, they are divided into several groups. All of them are considered important molecular drug targets due to their physiological roles, including the regulation of membrane potential or cell signaling. One of the recent trends in molecular pharmacology is the evaluation of the therapeutic potential of natural compounds and their derivatives, which can exhibit high specificity and effectiveness. Among the pharmaceuticals of plant origin, which are potassium channel modulators, flavonoids appear as a powerful group of biologically active substances. It is caused by their well-documented anti-oxidative, anti-inflammatory, anti-mutagenic, anti-carcinogenic, and antidiabetic effects on human health. Here, we focus on presenting the current state of knowledge about the possibilities of modulation of particular types of potassium channels by different flavonoids. Additionally, the biological meaning of the flavonoid-mediated changes in the activity of K+ channels will be outlined. Finally, novel promising directions for further research in this area will be proposed.
Topics: Humans; Potassium Channels; Hypoglycemic Agents; Potassium
PubMed: 36674825
DOI: 10.3390/ijms24021311 -
Annual Review of Physiology Feb 2024Novel variants encoding the BK K channel, are associated with a debilitating dyskinesia and epilepsy syndrome. Neurodevelopmental delay, cognitive disability, and brain... (Review)
Review
Novel variants encoding the BK K channel, are associated with a debilitating dyskinesia and epilepsy syndrome. Neurodevelopmental delay, cognitive disability, and brain and structural malformations are also diagnosed at lower incidence. More than half of affected individuals present with a rare negative episodic motor disorder, paroxysmal nonkinesigenic dyskinesia (PNKD3). The mechanistic relationship of PNKD3 to epilepsy and the broader spectrum of -associated symptomology is unknown. This review summarizes patient-associated variants within the BK channel structure, functional classifications, genotype-phenotype associations, disease models, and treatment. Patient and transgenic animal data suggest delineation of gain-of-function (GOF) and loss-of-function neurogenetic disease, validating two heterozygous alleles encoding GOF BK channels (D434G and N999S) as causing seizure and PNKD3. This discovery led to a variant-defined therapeutic approach for PNKD3, providing initial insight into the neurological basis. A comprehensive clinical definition of monogenic -linked disease and the neuronal mechanisms currently remain priorities for continued investigation.
Topics: Animals; Humans; Large-Conductance Calcium-Activated Potassium Channels; Channelopathies; Epilepsy; Chorea; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
PubMed: 37906945
DOI: 10.1146/annurev-physiol-030323-042845 -
Function (Oxford, England) 2022Ever since they were first observed in Purkinje fibers of the heart, funny channels have had close connections to potassium channels. Indeed, funny channels were...
Ever since they were first observed in Purkinje fibers of the heart, funny channels have had close connections to potassium channels. Indeed, funny channels were initially thought to produce a potassium current in the heart called . However, funny channels are completely unlike potassium channels in ways that make their contributions to the physiology of cells unique. An important difference is the greater ability for sodium to permeate funny channels. Although it does not flow through the funny channel as easily as does potassium, sodium does permeate well enough to allow for depolarization of cells following a strong hyperpolarization. This is critical for the function of funny channels in places like the heart and brain. Computational analyses using recent structures of the funny channels have provided a possible mechanism for their unusual permeation properties.
Topics: Potassium Channels; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Cyclic Nucleotide-Gated Cation Channels; Potassium; Sodium
PubMed: 36325512
DOI: 10.1093/function/zqac052 -
Epilepsia Open Jun 2024Variants in potassium channel-related genes are one of the most important mechanisms underlying abnormal neuronal excitation and disturbances in the cellular resting... (Review)
Review
Variants in potassium channel-related genes are one of the most important mechanisms underlying abnormal neuronal excitation and disturbances in the cellular resting membrane potential. These variants can cause different forms of epilepsy, which can seriously affect the physical and mental health of patients, especially those with refractory epilepsy or status epilepticus, which are common among pediatric patients and are potentially life-threatening. Variants in potassium ion channel-related genes have been reported in few studies; however, to our knowledge, no systematic review has been published. This study aimed to summarize the epilepsy phenotypes, functional studies, and pharmacological advances associated with different potassium channel gene variants to assist clinical practitioners and drug development teams to develop evidence-based medicine and guide research strategies. PubMed and Google Scholar were searched for relevant literature on potassium channel-related epilepsy reported in the past 5-10 years. Various common potassium ion channel gene variants can lead to heterogeneous epilepsy phenotypes, and functional effects can result from gene deletions and compound effects. Administration of select anti-seizure medications is the primary treatment for this type of epilepsy. Most patients are refractory to anti-seizure medications, and some novel anti-seizure medications have been found to improve seizures. Use of targeted drugs to correct aberrant channel function based on the type of potassium channel gene variant can be used as an evidence-based pathway to achieve precise and individualized treatment for children with epilepsy. PLAIN LANGUAGE SUMMARY: In this article, the pathogenesis and clinical characteristics of epilepsy caused by different types of potassium channel gene variants are reviewed in the light of the latest research literature at home and abroad, with the expectation of providing a certain theoretical basis for the diagnosis and treatment of children with this type of disease.
Topics: Humans; Potassium Channels; Epilepsy; Anticonvulsants
PubMed: 38560778
DOI: 10.1002/epi4.12934 -
Channels (Austin, Tex.) Jul 2017Potassium channels play important roles in microglia functions and thus constitute potential targets for the treatment of neurodegenerative diseases like Alzheimer,... (Review)
Review
Potassium channels play important roles in microglia functions and thus constitute potential targets for the treatment of neurodegenerative diseases like Alzheimer, Parkinson and stroke. However, uncertainty still prevails as to which potassium channels are expressed and at what levels in different species, how the expression pattern changes upon activation with M1 or M2 polarizing stimuli compared with more complex exposure paradigms, and - most importantly - how these findings relate to the in vivo situation. In this mini-review we discuss the functional potassium channel expression pattern in cultured neonatal mouse microglia in the light of data obtained previously from animal disease models and immunohistochemical studies and compare it with a recent study of adult human microglia isolated from epilepsy patients. Overall, microglial potassium channel expression is very plastic and possibly shows species differences and therefore should be studied carefully in each disease setting and respective animal models.
Topics: Animals; Cells, Cultured; Epilepsy; Humans; Mice; Microglia; Mutation; Neuronal Plasticity; Phenotype; Potassium Channels; Species Specificity
PubMed: 28277939
DOI: 10.1080/19336950.2017.1300738 -
International Journal of Molecular... Dec 2020The delayed rectifier potassium IKs channel is an important regulator of the duration of the ventricular action potential. Hundreds of mutations in the genes ( and )... (Review)
Review
The delayed rectifier potassium IKs channel is an important regulator of the duration of the ventricular action potential. Hundreds of mutations in the genes ( and ) encoding the IKs channel cause long QT syndrome (LQTS). LQTS is a heart disorder that can lead to severe cardiac arrhythmias and sudden cardiac death. A better understanding of the IKs channel (here called the KCNQ1/KCNE1 channel) properties and activities is of great importance to find the causes of LQTS and thus potentially treat LQTS. The KCNQ1/KCNE1 channel belongs to the superfamily of voltage-gated potassium channels. The KCNQ1/KCNE1 channel consists of both the pore-forming subunit KCNQ1 and the modulatory subunit KCNE1. KCNE1 regulates the function of the KCNQ1 channel in several ways. This review aims to describe the current structural and functional knowledge about the cardiac KCNQ1/KCNE1 channel. In addition, we focus on the modulation of the KCNQ1/KCNE1 channel and its potential as a target therapeutic of LQTS.
Topics: Animals; Arrhythmias, Cardiac; Humans; KCNQ1 Potassium Channel; Long QT Syndrome; Potassium Channels, Voltage-Gated
PubMed: 33322401
DOI: 10.3390/ijms21249440 -
The Journal of Cell Biology Jul 2014Potassium channels are pore-forming transmembrane proteins that regulate a multitude of biological processes by controlling potassium flow across cell membranes.... (Review)
Review
Potassium channels are pore-forming transmembrane proteins that regulate a multitude of biological processes by controlling potassium flow across cell membranes. Aberrant potassium channel functions contribute to diseases such as epilepsy, cardiac arrhythmia, and neuromuscular symptoms collectively known as channelopathies. Increasing evidence suggests that cancer constitutes another category of channelopathies associated with dysregulated channel expression. Indeed, potassium channel-modulating agents have demonstrated antitumor efficacy. Potassium channels regulate cancer cell behaviors such as proliferation and migration through both canonical ion permeation-dependent and noncanonical ion permeation-independent functions. Given their cell surface localization and well-known pharmacology, pharmacological strategies to target potassium channel could prove to be promising cancer therapeutics.
Topics: Cell Cycle; Cell Movement; Cell Proliferation; Humans; Models, Biological; Neoplasm Metastasis; Neoplasms; Potassium Channel Blockers; Potassium Channels; Tumor Microenvironment
PubMed: 25049269
DOI: 10.1083/jcb.201404136 -
Physiology (Bethesda, Md.) Sep 2022Voltage-gated potassium (Kv) channels each comprise four pore-forming α-subunits that orchestrate essential duties such as voltage sensing and K selectivity and... (Review)
Review
Voltage-gated potassium (Kv) channels each comprise four pore-forming α-subunits that orchestrate essential duties such as voltage sensing and K selectivity and conductance. In vivo, however, Kv channels also incorporate regulatory subunits-some Kv channel specific, others more general modifiers of protein folding, trafficking, and function. Understanding all the above is essential for a complete picture of the role of Kv channels in physiology and disease.
Topics: Humans; Potassium; Potassium Channels; Potassium Channels, Voltage-Gated; Protein Subunits
PubMed: 35797055
DOI: 10.1152/physiol.00005.2022 -
Biochimica Et Biophysica Acta Aug 2016In this review, we summarize our knowledge about mitochondrial potassium channels, with a special focus on unanswered questions in this field. The following potassium... (Review)
Review
In this review, we summarize our knowledge about mitochondrial potassium channels, with a special focus on unanswered questions in this field. The following potassium channels have been well described in the inner mitochondrial membrane: ATP-regulated potassium channel, Ca(2+)-activated potassium channel, the voltage-gated Kv1.3 potassium channel, and the two-pore domain TASK-3 potassium channel. The primary functional roles of these channels include regulation of mitochondrial respiration and the alteration of membrane potential. Additionally, they modulate the mitochondrial matrix volume and the synthesis of reactive oxygen species by mitochondria. Mitochondrial potassium channels are believed to contribute to cytoprotection and cell death. In this paper, we discuss fundamental issues concerning mitochondrial potassium channels: their molecular identity, channel pharmacology and functional properties. Attention will be given to the current problems present in our understanding of the nature of mitochondrial potassium channels. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.
Topics: Animals; Epithelial Cells; Gene Expression; Humans; Ion Transport; Mitochondria; Myocytes, Cardiac; Neurons; Organ Specificity; Plants; Potassium Channel Blockers; Potassium Channels, Calcium-Activated; Potassium Channels, Inwardly Rectifying; Potassium Channels, Tandem Pore Domain; Potassium Channels, Voltage-Gated; Saccharomyces cerevisiae; T-Lymphocytes; Trypanosomatina
PubMed: 26951942
DOI: 10.1016/j.bbabio.2016.03.007