Incidence of Allelic Polymorphisms of Genes Encoding Subunits ATP-Sensitive Potassium Channels (Ile337→Val and Glu23→Lys KCNJ11 Gene, and Ser1369→Ala ABCC8 Gene) in the Ukrainian Population

2018 ◽  
Vol 9 (1) ◽  
pp. 69-76
Author(s):  
Ruslan B. Strutynskyi ◽  
Roman A. Rovenets ◽  
Oleg V. Svarychevskyi ◽  
Viktor E. Dosenko
Keyword(s):  
Potassium Channels ◽  
Abcc8 Gene ◽  
Kcnj11 Gene ◽  
Genes Encoding

scholarly journals INCIDENCE OF ALLELIC POLYMORPHISMS OF GENES ENCODING SUBUNITS ATPSENSITIVE POTASSIUM CHANNELS (ILE337→VAL AND GLU23→LYS KCNJ11 GENE, AND SER1369→ALA ABCC8 GENE) IN THE UKRAINIAN POPULATION

2017 ◽  
Vol 63 (3) ◽  
pp. 3-8
Author(s):  
R.B. Strutynskyi ◽  
◽  
R.A. Rovenets ◽  
О.V. Svarychevskyi ◽  
V.E. Dosenko ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Abcc8 Gene ◽  
Kcnj11 Gene ◽  
Genes Encoding

scholarly journals Selective expression of KCNA5 and KCNB1 genes in gastric and colorectal carcinoma

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Azer Farah ◽  
Maria Kabbage ◽  
Salsabil Atafi ◽  
Amira Jaballah Gabteni ◽  
Mouadh Barbirou ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Cancer Progression ◽  
Clinical Stage ◽  
Inflammatory Cells ◽  
Tumour Cells ◽  
Malignant Tumours ◽  
Genes Encoding ◽  
First Time ◽  
Formalin Fixed

Abstract Background Gastric and colorectal cancers are the most common malignant tumours, leading to a significant number of cancer-related deaths worldwide. Recently, increasing evidence has demonstrated that cancer cells exhibit a differential expression of potassium channels and this can contribute to cancer progression. However, their expression and localisation at the somatic level remains uncertain. In this study, we have investigated the expression levels of KCNB1 and KCNA5 genes encoding ubiquitous Kv2.1 and Kv1.5 potassium channels in gastric and colorectal tumours. Methods Gastric and colorectal tumoral and peritumoral tissues were collected to evaluate the expression of KCNB1 and KCNA5 mRNA by quantitative PCR. Moreover, the immunohistochemical staining profile of Kv2.1 and Kv1.5 was assessed on 40 Formalin-Fixed and Paraffin-Embedded (FFPE) gastric carcinoma tissues. Differences in gene expression between tumoral and peritumoral tissues were compared statistically with the Mann-Whitney U test. The association between the clinicopathological features of the GC patients and the expression of both Kv proteins was investigated with χ2 and Fisher’s exact tests. Results The mRNA fold expression of KCNB1 and KCNA5 genes showed a lower mean in the tumoral tissues (0.06 ± 0.17, 0.006 ± 0.009) compared to peritumoral tissues (0.08 ± 0.16, 0.16 ± 0.48, respectively) without reaching the significance rate (p = 0.861, p = 0.152, respectively). Interestingly, Kv2.1 and Kv1.5 immunostaining was detectable and characterised by a large distribution in peritumoral and tumoral epithelial cells. More interestingly, inflammatory cells were also stained. Surprisingly, Kv2.1 and Kv1.5 staining was undoubtedly and predominantly detected in the cytoplasm compartment of tumour cells. Indeed, the expression of Kv2.1 in tumour cells revealed a significant association with the early gastric cancer clinical stage (p = 0.026). Conclusion The data highlight, for the first time, the potential role of Kv1.5 and Kv2.1 in gastrointestinal-related cancers and suggests they may be promising prognostic markers for these tumours.

scholarly journals Heritable arrhythmias associated with abnormal function of cardiac potassium channels

2020 ◽  
Vol 116 (9) ◽  
pp. 1542-1556 ◽  
Author(s):  
Lia Crotti ◽  
Katja E Odening ◽  
Michael C Sanguinetti
Keyword(s):  
Potassium Channels ◽  
Genetic Basis ◽  
Resting Membrane Potential ◽  
Therapeutic Approaches ◽  
Functional Roles ◽  
Cellular Models ◽  
Sodium Calcium ◽  
Disease Mechanisms ◽  
Genes Encoding ◽  
Action Potential Repolarization

Abstract Cardiomyocytes express a surprisingly large number of potassium channel types. The primary physiological functions of the currents conducted by these channels are to maintain the resting membrane potential and mediate action potential repolarization under basal conditions and in response to changes in the concentrations of intracellular sodium, calcium, and ATP/ADP. Here, we review the diversity and functional roles of cardiac potassium channels under normal conditions and how heritable mutations in the genes encoding these channels can lead to distinct arrhythmias. We briefly review atrial fibrillation and J-wave syndromes. For long and short QT syndromes, we describe their genetic basis, clinical manifestation, risk stratification, traditional and novel therapeutic approaches, as well as insights into disease mechanisms provided by animal and cellular models.

Neonatal diabetes mellitus: the effectiveness of therapy with sulfonylurea preparations depending on the type of mutation in the KCNJ11 gene

2014 ◽  
Vol 60 (1) ◽  
pp. 57-63
Author(s):  
A O Emelyanov ◽  
T L Kuraeva ◽  
S A Prokofiev ◽  
E D Medvedeva ◽  
V A Peterkova
Keyword(s):  
Diabetes Mellitus ◽  
Potassium Channels ◽  
Beta Cells ◽  
Clinical Significance ◽  
Newborn Infants ◽  
Neonatal Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Metabolic Processes ◽  
Kcnj11 Gene ◽  
The Relationship

Neonatal diabetes mellitus (NDM) develops within the first 6 months of life. It occurs with a frequency of 1 cases per 300,000 - 500,000 newborn infants. Pathogenesis of NDM involves over 10 different genes. Of greatest clinical significance are mutations in KCNJII and ABCC8 genes responsible for the activity of ATP-dependent potassium channels and regulating their activation. It was shown that the intake of oral sulfonylurea (SU) preparations results in the closure of these channels and thereby stimulates the release of insulin from beta-cells. For this reason, SU therapy can be applied as an alternative to insulin injections. SU preparations ensure the efficacious control of metabolic processes and substitute insulin in the majority of the cases of transient and permanent NDM associated with mutations in KCNJII and ABCC8 genes. The original observations demonstrating the relationship between the type of mutation in the KCNJII gene and the dose of SU preparations are presented.

scholarly journals Revisiting the Large-Conductance Calcium-Activated Potassium (BKCa) Channels in the Pulmonary Circulation

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1629
Author(s):  
Divya Guntur ◽  
Horst Olschewski ◽  
Péter Enyedi ◽  
Réka Csáki ◽  
Andrea Olschewski ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Potassium Channels ◽  
Pulmonary Circulation ◽  
Hypoxic Pulmonary Vasoconstriction ◽  
Free Calcium ◽  
Bkca Channel ◽  
Lung Pathology ◽  
Open Probability ◽  
Bkca Channels ◽  
Genes Encoding

Potassium ion concentrations, controlled by ion pumps and potassium channels, predominantly govern a cell′s membrane potential and the tone in the vessels. Calcium-activated potassium channels respond to two different stimuli-changes in voltage and/or changes in intracellular free calcium. Large conductance calcium-activated potassium (BKCa) channels assemble from pore forming and various modulatory and auxiliary subunits. They are of vital significance due to their very high unitary conductance and hence their ability to rapidly cause extreme changes in the membrane potential. The pathophysiology of lung diseases in general and pulmonary hypertension, in particular, show the implication of either decreased expression and partial inactivation of BKCa channel and its subunits or mutations in the genes encoding different subunits of the channel. Signaling molecules, circulating humoral molecules, vasorelaxant agents, etc., have an influence on the open probability of the channel in pulmonary arterial vascular cells. BKCa channel is a possible therapeutic target, aimed to cause vasodilation in constricted or chronically stiffened vessels, as shown in various animal models. This review is a comprehensive collation of studies on BKCa channels in the pulmonary circulation under hypoxia (hypoxic pulmonary vasoconstriction; HPV), lung pathology, and fetal to neonatal transition, emphasising pharmacological interventions as viable therapeutic options.

scholarly journals Mitochondrial potassium channels: A novel calcitriol target

2022 ◽  
Vol 27 (1) ◽  
Author(s):  
Anna M. Olszewska ◽  
Adam K. Sieradzan ◽  
Piotr Bednarczyk ◽  
Adam Szewczyk ◽  
Michał A. Żmijewski
Keyword(s):  
Vitamin D ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Mitochondrial Membrane ◽  
Human Keratinocytes ◽  
Inner Mitochondrial Membrane ◽  
Open Probability ◽  
Expression Of Genes ◽  
High Calcium ◽  
Genes Encoding

Abstract Background Calcitriol (an active metabolite of vitamin D) modulates the expression of hundreds of human genes by activation of the vitamin D nuclear receptor (VDR). However, VDR-mediated transcriptional modulation does not fully explain various phenotypic effects of calcitriol. Recently a fast non-genomic response to vitamin D has been described, and it seems that mitochondria are one of the targets of calcitriol. These non-classical calcitriol targets open up a new area of research with potential clinical applications. The goal of our study was to ascertain whether calcitriol can modulate mitochondrial function through regulation of the potassium channels present in the inner mitochondrial membrane. Methods The effects of calcitriol on the potassium ion current were measured using the patch-clamp method modified for the inner mitochondrial membrane. Molecular docking experiments were conducted in the Autodock4 program. Additionally, changes in gene expression were investigated by qPCR, and transcription factor binding sites were analyzed in the CiiiDER program. Results For the first time, our results indicate that calcitriol directly affects the activity of the mitochondrial large-conductance Ca2+-regulated potassium channel (mitoBKCa) from the human astrocytoma (U-87 MG) cell line but not the mitochondrial calcium-independent two-pore domain potassium channel (mitoTASK-3) from human keratinocytes (HaCaT). The open probability of the mitoBKCa channel in high calcium conditions decreased after calcitriol treatment and the opposite effect was observed in low calcium conditions. Moreover, using the AutoDock4 program we predicted the binding poses of calcitriol to the calcium-bound BKCa channel and identified amino acids interacting with the calcitriol molecule. Additionally, we found that calcitriol influences the expression of genes encoding potassium channels. Such a dual, genomic and non-genomic action explains the pleiotropic activity of calcitriol. Conclusions Calcitriol can regulate the mitochondrial large-conductance calcium-regulated potassium channel. Our data open a new chapter in the study of non-genomic responses to vitamin D with potential implications for mitochondrial bioenergetics and cytoprotective mechanisms.

scholarly journals Genetic Variation in Genes Encoding Airway Epithelial Potassium Channels Is Associated with Chronic Rhinosinusitis in a Pediatric Population

PLoS ONE ◽  
2014 ◽  
Vol 9 (3) ◽  
pp. e89329 ◽  
Author(s):  
Michael T. Purkey ◽  
Jin Li ◽  
Frank Mentch ◽  
Struan F. A. Grant ◽  
Martin Desrosiers ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Potassium Channels ◽  
Chronic Rhinosinusitis ◽  
Pediatric Population ◽  
Airway Epithelial ◽  
Genes Encoding

scholarly journals Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies

2021 ◽  
Author(s):  
Karen W. Gripp ◽  
Sarah F. Smithson ◽  
Ingrid J. Scurr ◽  
Julia Baptista ◽  
Anirban Majumdar ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Developmental Disorders ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Gingival Enlargement ◽  
Genes Encoding ◽  
Human Disorders ◽  
The Central Nervous System ◽  
Encoding Genes ◽  
Increased Activity

AbstractDecreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K+ channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann–Laband and Temple–Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K+ conductance, referred to as syndromic neurodevelopmental K+ channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.

scholarly journals Novel Compound Heterozygous Variants of the ABCC8 Gene Warrant Identification of Pancreatic Histology in Infant with Diazoxide-unresponsive Congenital Hyperinsulinism

Children ◽  
2021 ◽  
Vol 8 (10) ◽  
pp. 836
Author(s):  
Rana Al Balwi ◽  
Dalal Bubshait ◽  
Raed Al Nefily ◽  
Omar Al Ghamdi
Keyword(s):  
Autosomal Recessive ◽  
Severe Hypoglycemia ◽  
Katp Channels ◽  
Compound Heterozygous ◽  
Congenital Hyperinsulinism ◽  
Abcc8 Gene ◽  
Genes Encoding ◽  
One Year ◽  
The One ◽  
Compound Heterozygous Variants

Congenital hyperinsulinism (CHI) is characterized by dysregulated insulin secretion, resulting in severe hypoglycemia. Mutations in the ABCC8 and KCNJ11 genes encoding KATP channels in beta cells of the pancreas are common among patients with CHI. Autosomal recessive CHI with diffuse involvement is the most common type of CHI among Saudi patients. It is relatively common for patients with autosomal recessive CHI to be medically unresponsive and undergo pancreatectomy. In this case report, we describe novel compound heterozygous variants in the ABCC8 gene in a Saudi infant that caused diazoxide-unresponsive CHI. The variants included a monoallelic paternally inherited variant that has been previously reported to cause a focal form of CHI and a maternally inherited variant of unknown significance (VUS). The severity of CHI in this patient was mild over the one-year follow-up period, with a near-optimal glycemic response on a low dose of octreotide. We suspected an atypical subtype of histological involvement in the patient. In this report, we highlight the phenotypic spectrum of novel compound heterozygous variants in a patient with CHI and consider that the report can help establish the pathogenicity of the VUS.

scholarly journals Genotyping of ABCC8, KCNJ11, and HADH in Iranian Infants with Congenital Hyperinsulinism

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Somayyeh Hashemian ◽  
Reza Jafarzadeh Esfehani ◽  
Siroos Karimdadi ◽  
Nosrat Ghaemi ◽  
Peyman Eshraghi ◽  
...  
Keyword(s):  
Mutational Analysis ◽  
Genetic Diagnosis ◽  
Case Series ◽  
Missense Variant ◽  
Congenital Hyperinsulinism ◽  
Biochemical Tests ◽  
Functional Studies ◽  
Pathogenic Variants ◽  
Abcc8 Gene ◽  
Kcnj11 Gene

Background. Congenital hyperinsulinism (CHI) is a heterogeneous disease with various underlying genetic causes. Among different genes considered effective in the development of CHI, ABCC8, KCNJ11, and HADH genes are among the important genes, especially in a population with a considerable rate of consanguineous marriage. Mutational analysis of these genes guides clinicians to better treatment and prediction of prognosis for this rare disease. The present study aimed to evaluate genetic variants in ABCC8, KCNJ11, and HADH genes as causative genes for CHI in the Iranian population. Methods. The present case series took place in Mashhad, Iran, within 11 years. Every child who had a clinical phenotype and confirmatory biochemical tests of CHI enrolled in this study. Variants in ABCC8, KCNJ11, and HADH genes were analyzed by the polymerase chain reaction and sequencing in our patients. Results. Among 20 pediatric patients, 16 of them had variants in ABCC8, KCNJ11, and HADH genes. The mean age of genetic diagnosis was 18.6 days. A homozygous missense (c.2041-21G > A) mutation in the ABCC8 gene was seen in three infants. Other common variants were frameshift variants (c.3438dup) in the ABCC8 gene and a missense variant (c.287-288delinsTG) in the KCNJ11 gene. Most of the variants in our population were still categorized as variants of unknown significance and only 7 pathogenic variants were present. Conclusion. Most variants were located in the ABCC8 gene in our population. Because most of the variants in our population are not previously reported, performing further functional studies is warranted.

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