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Neuron Nov 2001What is the moving part that switches an ion channel's current on and off? In this issue of Neuron del Camino and Yellen (2001) exploit scanning cysteine mutagenesis and... (Review)
Review
What is the moving part that switches an ion channel's current on and off? In this issue of Neuron del Camino and Yellen (2001) exploit scanning cysteine mutagenesis and sulfhydryl reagents to show that the intracellular end of the S6 helices forms a mechanical gate for the Shaker potassium channel.
Topics: Animals; Ion Channel Gating; Mutagenesis; Neurons; Potassium Channels
PubMed: 11719196
DOI: 10.1016/s0896-6273(01)00509-8 -
Cardiac Electrophysiology Clinics Jun 2016Heart disease produces substantial remodeling of K(+) channels that in general promotes arrhythmia occurrence. In the case of ventricular arrhythmias, K(+) channel... (Review)
Review
Heart disease produces substantial remodeling of K(+) channels that in general promotes arrhythmia occurrence. In the case of ventricular arrhythmias, K(+) channel remodeling contributes to the arrhythmic risk and increases vulnerability to torsades de pointes with K(+) channel inhibiting drugs. Atrial K(+) channel remodeling caused by atrial fibrillation promotes arrhythmia stability and presents opportunities for the development of new drugs targeting atrial inward rectifier K(+) currents. A better understanding of K(+) channel remodeling will help clinicians to appreciate arrhythmia mechanisms and determinants in a variety of clinical situations and to better manage arrhythmia therapy in patients with heart disease.
Topics: Action Potentials; Arrhythmias, Cardiac; Cardiovascular Physiological Phenomena; Humans; Potassium Channel Blockers; Potassium Channels
PubMed: 27261825
DOI: 10.1016/j.ccep.2016.01.006 -
Biomedicine & Pharmacotherapy =... Jun 2023Potassium channels play an important role in human physiological function. Recently, various molecular mechanisms have implicated abnormal functioning of potassium... (Review)
Review
Potassium channels play an important role in human physiological function. Recently, various molecular mechanisms have implicated abnormal functioning of potassium channels in the proliferation, migration, invasion, apoptosis, and cancer stem cell phenotype formation. Potassium channels also mediate the association of tumor cells with the tumor microenvironment. Meanwhile, potassium channels are important targets for cancer chemotherapy. A variety of drugs exert anti-cancer effects by modulating potassium channels in tumor cells. Therefore, there is a need to understand how potassium channels participate in tumor development and progression, which could reveal new, novel targets for cancer diagnosis and treatment. This review summarizes the roles of voltage-gated potassium channels, calcium-activated potassium channels, inwardly rectifying potassium channels, and two-pore domain potassium channels in tumorigenesis and the underlying mechanism of potassium channel-targeted drugs. Therefore, the study lays the foundation for rational and effective drug design and individualized clinical therapeutics.
Topics: Humans; Potassium Channels; Potassium Channels, Voltage-Gated; Potassium Channels, Calcium-Activated; Cell Transformation, Neoplastic; Neoplasms; Tumor Microenvironment
PubMed: 37031494
DOI: 10.1016/j.biopha.2023.114673 -
Current Opinion in Endocrinology,... Jun 2013To summarize and discuss data from recent studies implicating mutations in potassium channel genes in the pathogenesis of primary aldosteronism. (Review)
Review
PURPOSE OF REVIEW
To summarize and discuss data from recent studies implicating mutations in potassium channel genes in the pathogenesis of primary aldosteronism.
RECENT FINDINGS
Potassium channel gene variants are associated with the primary aldosteronism phenotype in animals (Kcnma1, TASK-1, and TASK-3) and humans (HERG and KCNJ5). Germline KCNJ5 mutations cause bilateral, familial primary aldosteronism with variable severity and genotype:phenotype correlations. Somatic KCNJ5 mutations occur in approximately 40% of aldosterone-producing adenomas, and are associated with younger age, female sex, more severe primary aldosteronism, lack of responsiveness of plasma aldosterone to upright posture, and zona fasciculata histology. Of five so far described, G151R and L168R are by far the most common. KCNJ5 mutations lead to reduced K⁺/Na⁺ channel selectivity and Na⁺ influx, predisposing to cell membrane depolarization, increased calcium influx, increased expression of genes promoting aldosterone synthesis, and increased aldosterone production by adrenocortical cells. How they lead to adrenal cell proliferation and tumor development is less well understood.
SUMMARY
These findings shed considerable light on the pathophysiology of primary aldosteronism with the potential to lead to new diagnostic approaches and treatments.
Topics: Amino Acid Substitution; Animals; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Humans; Hyperaldosteronism; Mutation; Potassium Channels; Severity of Illness Index
PubMed: 23426162
DOI: 10.1097/MED.0b013e32835ef2fd -
Trends in Neurosciences Jun 2000
Review
Topics: Animals; Ion Channel Gating; Nerve Tissue Proteins; Neurons; Potassium Channels; Potassium Channels, Tandem Pore Domain; Protein Structure, Tertiary
PubMed: 10838588
DOI: 10.1016/s0166-2236(00)01592-7 -
Physiology (Bethesda, Md.) Feb 2008Phosphorylation of potassium channels affects their function and plays a major role in regulating cell physiology. Here, we review previous studies of potassium channel... (Review)
Review
Phosphorylation of potassium channels affects their function and plays a major role in regulating cell physiology. Here, we review previous studies of potassium channel phosphorylation, focusing first on studies employing site-directed mutagenesis of recombinant channels expressed in heterologous cells. We then discuss recent mass spectrometric-based approaches to identify and quantify phosphorylation at specific sites on native and recombinant potassium channels, and newly developed mass spectrometric-based techniques that may prove beneficial to future studies of potassium channel phosphorylation, its regulation, and its mechanism of channel modulation.
Topics: Animals; Humans; Ion Channel Gating; Mass Spectrometry; Membrane Potentials; Models, Molecular; Mutation; Phosphorylation; Potassium Channels; Protein Conformation; Protein Transport; Recombinant Proteins; Time Factors
PubMed: 18268365
DOI: 10.1152/physiol.00031.2007 -
Cellular and Molecular Life Sciences :... Oct 2015Potassium channels ubiquitously exist in nearly all kingdoms of life and perform diverse but important functions. Since the first atomic structure of a prokaryotic... (Review)
Review
Potassium channels ubiquitously exist in nearly all kingdoms of life and perform diverse but important functions. Since the first atomic structure of a prokaryotic potassium channel (KcsA, a channel from Streptomyces lividans) was determined, tremendous progress has been made in understanding the mechanism of potassium channels and channels conducting other ions. In this review, we discuss the structure of various kinds of potassium channels, including the potassium channel with the pore-forming domain only (KcsA), voltage-gated, inwardly rectifying, tandem pore domain, and ligand-gated ones. The general properties shared by all potassium channels are introduced first, followed by specific features in each class. Our purpose is to help readers to grasp the basic concepts, to be familiar with the property of the different domains, and to understand the structure and function of the potassium channels better.
Topics: Dimerization; Ion Channel Gating; Models, Molecular; Potassium Channels; Protein Structure, Tertiary; Species Specificity
PubMed: 26070303
DOI: 10.1007/s00018-015-1948-5 -
Cardiovascular Drugs and Therapy Mar 1995The potassium-channel openers comprise a large number of molecules that can be classified into three basic groups: (1) agents like levcromakalim that open a... (Review)
Review
The potassium-channel openers comprise a large number of molecules that can be classified into three basic groups: (1) agents like levcromakalim that open a small-conductance (10-30 pS) glibenclamide-sensitive K+ channel currently known as the ATP-sensitive K+ channel, KATP; (2) hybrid molecules, such as nicorandil, that open KATP channels and that also activate the enzyme-soluble guanylate cyclase; (3) molecules like dehydrosaponin 1 that open the large-conductance (100-150 pS) calcium-dependent K+ channel, BKCa. K(+)-channel openers in groups 1 and 2 are most potent on smooth muscle, but KATP channels in cardiac muscle, neurones and the pancreatic beta cell are also affected. In vivo, moderate to high doses produce a fall in diastolic pressure with reflex tachycardia; low doses may exert selective dilator effects on specific vascular beds with little effect on systemic pressure. In vitro, all smooth muscles are relaxed with loss of spontaneous electric and mechanical activity; hyperpolarization to the region of EK is often observed. These effects can be antagonized by glibenclamide and also by imidazolines and guanidines, such as phentolamine, guanethidine, and antazoline, agents that also inhibit the smooth muscle delayed rectifier channel, KV. The mode and site of action of the group 1 and 2 K(+)-channel openers is the subject of intense study. Irrespective of their specific mode of action, the K(+)-channel openers, especially the hybrid molecules such as nicorandil, constitute a novel and promising approach to the treatment of cardiovascular disease.
Topics: Animals; Humans; Potassium Channels
PubMed: 7647022
DOI: 10.1007/BF00878465 -
Molecular Interventions Jun 2001Voltage-gated potassium channels provide tightly Controlled, ion-specific pathways across membranes and are key to the normal function of nerves muscles. They arise from... (Review)
Review
Voltage-gated potassium channels provide tightly Controlled, ion-specific pathways across membranes and are key to the normal function of nerves muscles. They arise from the assembly of four pore-forming proteins called alpha-subunits. To attain the properties of native currents, alpha-subunits interact with additional molecules such as the mink-related peptides (MiRPs), single-transmembrane subunits encoded by the KCNE genes. Significantly, mutations in KCNE 1, 2 and 3 have been linked either to life-threatening cardiac arrhythmia or a disorder of skeletal muscle, familial periodic paralysis. The capacity of MiRPs to partner with multiple alpha-subunits in experimental cells appears to reflect still undiscovered roles for the KCNE-encoded peptides in vivo. Here, we consider these unique peptides in health disease and discuss future research directions.
Topics: Amino Acid Sequence; Animals; Arrhythmias, Cardiac; Cation Transport Proteins; Electric Conductivity; Ether-A-Go-Go Potassium Channels; Forecasting; Humans; Ion Channel Gating; Models, Biological; Molecular Sequence Data; Mutation, Missense; Potassium Channels; Potassium Channels, Voltage-Gated; Protein Structure, Tertiary; Protein Subunits; Sequence Homology, Amino Acid
PubMed: 14993329
DOI: No ID Found -
Biomolecules Aug 2020Mitochondrial potassium channels have been described as important factors in cell pro-life and death phenomena. The activation of mitochondrial potassium channels, such... (Review)
Review
Mitochondrial potassium channels have been described as important factors in cell pro-life and death phenomena. The activation of mitochondrial potassium channels, such as ATP-regulated or calcium-activated large conductance potassium channels, may have cytoprotective effects in cardiac or neuronal tissue. It has also been shown that inhibition of the mitochondrial Kv1.3 channel may lead to cancer cell death. Hence, in this paper, we examine the concept of the druggability of mitochondrial potassium channels. To what extent are mitochondrial potassium channels an important, novel, and promising drug target in various organs and tissues? The druggability of mitochondrial potassium channels will be discussed within the context of channel molecular identity, the specificity of potassium channel openers and inhibitors, and the unique regulatory properties of mitochondrial potassium channels. Future prospects of the druggability concept of mitochondrial potassium channels will be evaluated in this paper.
Topics: Animals; Drug Design; Humans; Mitochondria; Molecular Targeted Therapy; Potassium Channels
PubMed: 32824877
DOI: 10.3390/biom10081200