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Genome Biology 2000Potassium channels, tetrameric integral membrane proteins that form aqueous pores through which K+ can flow, are found in virtually all organisms; the genomes of humans,... (Review)
Review
Potassium channels, tetrameric integral membrane proteins that form aqueous pores through which K+ can flow, are found in virtually all organisms; the genomes of humans, Drosophila, and Caenorhabditis elegans contain 30-100 K+ channel genes each. The structure of a bacterial K+ channel, sequence comparisons with other channels and electrophysiological measurements have enabled conclusions about the mechanism of gating and ion flow to be drawn for many other channels.
Topics: Animals; Evolution, Molecular; Humans; Ion Channel Gating; Models, Molecular; Potassium Channels; Protein Conformation
PubMed: 11178249
DOI: 10.1186/gb-2000-1-4-reviews0004 -
Progress in Clinical and Biological... 1990
Review
Topics: Animals; Barium; Humans; Ion Channel Gating; Potassium Channels; Tetraethylammonium Compounds
PubMed: 2408065
DOI: No ID Found -
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 -
Japanese Journal of Pharmacology 1992
Review
Topics: Animals; Humans; Muscle, Smooth, Vascular; Potassium Channels
PubMed: 1507539
DOI: No ID Found -
The Indian Journal of Medical Research Mar 2009Ion channels present in the plasma membrane and intracellular organelles of all cells, play an important role in maintaining cellular integrity, smooth muscle... (Review)
Review
Ion channels present in the plasma membrane and intracellular organelles of all cells, play an important role in maintaining cellular integrity, smooth muscle contraction, secretion of hormones and neurotransmitters. Among the ion channels, potassium channels (K(+)) are the most abundant having important role in cardiac repolarization, smooth muscle relaxation and insulin release. These are also involved in the regulation of physiological functions like gastrointestinal peristalsis. These channels are the most diverse of all ion channels and are coded by at least 75 genes. Moreover, these have different subunits which co-assemble to form diverse functional channels. Abnormalities in K(+) channels are associated with diseases like long QT syndrome, Anderson Tawil syndrome, epilepsy, type 2 diabetes mellitus, etc. A number of naturally occurring as well as synthetic compounds have been identified that modulate the opening and closure of K(ATP) Channels. Some of the currently available K(+) channel modulators like sulphonylureas, minoxidil, amiodarone, etc. lack tissue selectivity and have adverse effects. Hence, the success of K(ATP) channel modulators depend on their tissue selectivity. Molecular level studies are needed to understand the type of K(+) channels as this can lead to the development of newer drugs with tissue selectivity for various diseases.
Topics: Animals; Brain; Diabetes Mellitus, Type 2; Heart; Heart Diseases; Humans; Potassium Channel Blockers; Potassium Channels
PubMed: 19491413
DOI: No ID Found -
Clinical and Experimental Pharmacology... Apr 20021. One essential role for potassium channels in vascular smooth muscle is to buffer cell excitation and counteract vasoconstrictive influences. Several molecular... (Review)
Review
1. One essential role for potassium channels in vascular smooth muscle is to buffer cell excitation and counteract vasoconstrictive influences. Several molecular mechanisms regulate potassium channel function. The interaction of these mechanisms may be one method for fine-tuning potassium channel activity in response to various physiological and pathological challenges. 2. The most prevalent K+ channels in vascular smooth muscle are large-conductance calcium- and voltage-sensitive channels (maxi-K channels) and voltage-gated channels (Kv channels). Both channel types are complex molecular structures consisting of a pore-forming alpha-subunit and an ancillary beta-subunit. The maxi-K and Kv channel alpha-subunits assemble as tetramers and have S4 transmembrane domains that represent the putative voltage sensor. While most vascular smooth muscle cells identified to date contain both maxi-K and Kv channels, the expression of individual alpha-subunit isoforms and beta-subunit association occurs in a tissue-specific manner, thereby providing functional specificity. 3. The maxi-K channel alpha-subunit derives its molecular diversity by alternative splicing of a single-gene transcript to yield multiple isoforms that differ in their sensitivity to intracellular Ca2+ and voltage, cell surface expression and post- translational modification. The ability of this channel to assemble as a homo- or heterotetramer allows for fine-tuning control to intracellular regulators. Another level of diversity for this channel is in its association with accessory beta-subunits. Multiple beta-subunits have been identified that can arise either from separate genes or alternative splicing of a beta-subunit gene. The maxi-K channel beta-subunits modulate the channel's Ca2+ and voltage sensitivity and kinetic and pharmacological properties. 4. The Kv channel alpha-subunit derives its diverse nature by the expression of several genes. Similar to the maxi-K channel, this channel has been shown to assemble as a homo- and heterotetramer, which can significantly change the Kv current phenotype in a given cell type. Association with a number of the ancillary beta-subunits affects Kv channel function in several ways. Beta-subunits can induce inactivating properties and act as chaperones, thereby regulating channel cell-surface expression and current kinetics.
Topics: Animals; Humans; Muscle, Smooth, Vascular; Potassium Channels; Protein Isoforms
PubMed: 11985543
DOI: 10.1046/j.1440-1681.2002.03651.x -
The Journal of Biological Chemistry Nov 2018Potassium channels that exhibit the property of inward rectification (Kir channels) are present in most cells. Cloning of the first Kir channel genes 25 years ago led to... (Review)
Review
Potassium channels that exhibit the property of inward rectification (Kir channels) are present in most cells. Cloning of the first Kir channel genes 25 years ago led to recognition that inward rectification is a consequence of voltage-dependent block by cytoplasmic polyamines, which are also ubiquitously present in animal cells. Upon cellular depolarization, these polycationic metabolites enter the Kir channel pore from the intracellular side, blocking the movement of K ions through the channel. As a consequence, high K conductance at rest can provide very stable negative resting potentials, but polyamine-mediated blockade at depolarized potentials ensures, for instance, the long plateau phase of the cardiac action potential, an essential feature for a stable cardiac rhythm. Despite much investigation of the polyamine block, where exactly polyamines get to within the Kir channel pore and how the steep voltage dependence arises remain unclear. This Minireview will summarize current understanding of the relevance and molecular mechanisms of polyamine block and offer some ideas to try to help resolve the fundamental issue of the voltage dependence of polyamine block.
Topics: Ion Transport; Polyamines; Potassium; Potassium Channels; Protein Conformation
PubMed: 30333230
DOI: 10.1074/jbc.TM118.003344 -
Current Biology : CB Sep 1994Recent discoveries indicate that potassium channel beta subunits can have profound functional roles, particularly in determining the channel inactivation properties. (Review)
Review
Recent discoveries indicate that potassium channel beta subunits can have profound functional roles, particularly in determining the channel inactivation properties.
Topics: Animals; Cattle; Cloning, Molecular; Female; Kinetics; Oocytes; Oxidation-Reduction; Potassium Channel Blockers; Potassium Channels; Protein Conformation; Rats; Xenopus
PubMed: 7865026
DOI: 10.1016/s0960-9822(00)00187-1 -
Chemical Biology & Drug Design Jan 2014Potassium channels participate in many critical biological functions and play important roles in a variety of diseases. In recent years, many significant discoveries... (Review)
Review
Potassium channels participate in many critical biological functions and play important roles in a variety of diseases. In recent years, many significant discoveries have been made which motivate us to review these achievements. The focus of our review is mainly on three aspects. Firstly, we try to summarize the latest developments in structure determinants and regulation mechanism of all types of potassium channels. Secondly, we review some diseases induced by or related to these channels. Thirdly, both qualitative and quantitative approaches are utilized to analyze structural features of modulators of potassium channels. Our analyses further prove that modulators possess some certain natural-product scaffolds. And pharmacokinetic parameters are important properties for organic molecules. Besides, with in silico methods, some features that can be used to differentiate modulators are derived. There is no doubt that all these studies on potassium channels as possible pharmaceutical targets will facilitate future translational research. All the strategies developed in this review could be extended to studies on other ion channels and proteins as well.
Topics: Biological Products; Half-Life; Heart Diseases; Humans; Molecular Dynamics Simulation; Neurodegenerative Diseases; Potassium Channel Blockers; Potassium Channels; Protein Structure, Tertiary
PubMed: 24119115
DOI: 10.1111/cbdd.12237 -
Handbook of Experimental Pharmacology 2006Cardiac K+ channels play an important role in the regulation of the shape and duration of the action potential. They have been recognized as targets for the actions of... (Review)
Review
Cardiac K+ channels play an important role in the regulation of the shape and duration of the action potential. They have been recognized as targets for the actions of neurotransmitters, hormones, and anti-arrhythmic drugs that prolong the action potential duration (APD) and increase refractoriness. However, pharmacological therapy, often for the purpose of treating syndromes unrelated to cardiac disease, can also increase the vul- nerability of some patients to life-threatening rhythm disturbances. This may be due to an underlying propensity stemming from inherited mutations or polymorphisms, or structural abnormalities that provide a substrate allowing for the initiation of arrhythmic triggers. A number of pharmacological agents that have proved useful in the treatment of allergic reactions, gastrointestinal disorders, and psychotic disorders, among others, have been shown to reduce repolarizing K+ currents and prolong the Q-T interval on the electrocardiogram. Understanding the structural determinants of K+ channel blockade might provide new insights into the mechanism and rate-dependent effects of drugs on cellular physiology. Drug-induced disruption of cellular repolarization underlies electrocardiographic abnormalities that are diagnostic indicators of arrhythmia susceptibility.
Topics: Action Potentials; Animals; Arrhythmias, Cardiac; Delayed Rectifier Potassium Channels; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Heart; Humans; Intermediate-Conductance Calcium-Activated Potassium Channels; KCNQ1 Potassium Channel; Long QT Syndrome; Potassium Channel Blockers; Potassium Channels; Potassium Channels, Voltage-Gated; Structure-Activity Relationship
PubMed: 16610343
DOI: 10.1007/3-540-29715-4_5