4.7 Review

Channelopathy of small- and intermediate-conductance Ca2+-activated K+ channels

Related references

Note: Only part of the references are listed.
Article Genetics & Heredity

Zimmermann-Laband syndrome in monozygotic twins with a mild neurobehavioral phenotype lacking gingival overgrowth-A case report of a novel KCNN3 gene variant

Martin Schwarz et al.

Summary: Zimmermann-Laband syndrome is a rare genetic disorder characterized by gingival hypertrophy, nail abnormalities, intellectual disabilities, hypertrichosis, and distinctive facial features. A pair of female monozygotic twins with a novel pathogenic variant in the KCNN3 gene showed mild symptoms compared to previous cases, highlighting the importance of proper genetic counseling for patients and their families.

AMERICAN JOURNAL OF MEDICAL GENETICS PART A (2022)

Review Neurosciences

Electrophysiological Studies Support Utility of Positive Modulators of SK Channels for the Treatment of Spinocerebellar Ataxia Type 2

Polina A. Egorova et al.

Summary: Spinocerebellar ataxia type 2 (SCA2) is an incurable hereditary disorder characterized by cerebellar degeneration and ataxic symptoms. Mutations in the ATXN2 gene lead to impaired RNA metabolism and loss of function of the ataxin-2 protein, while also enhancing calcium signaling. Abnormal activity of cerebellar Purkinje cells (PCs) is associated with various ataxic disorders. Activation of SK channels has shown promising results in improving motor function and PC morphology in SCA2 mice, suggesting it as a potential therapeutic approach for SCA2 and other diseases with cerebellar degeneration.

CEREBELLUM (2022)

Article Chemistry, Medicinal

Structure-Activity Relationship Study of Subtype-Selective Positive Modulators of KCa2 Channels

Naglaa Salem El-Sayed et al.

Summary: A series of modified CyPPA analogues were synthesized and studied for their potentiation of K(Ca)2 channel activity. Two compounds showed potential therapeutic usefulness in an SCA2 mouse model by normalizing abnormal firing of Purkinje cells.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

Article Pharmacology & Pharmacy

Subtype-selective positive modulation of KCa2 channels depends on the HA/HB helices

Young-Woo Nam et al.

Summary: The selectivity of CyPPA among K(Ca)2 and K(Ca)3.1 channel subtypes relies on the HA/HB helices.

BRITISH JOURNAL OF PHARMACOLOGY (2022)

Article Cell Biology

Channelopathy-causing mutations in the S45A/S45B and HA/HB helices of KCa2.3 and KCa3.1 channels alter their apparent Ca2+ sensitivity

Razan Orfali et al.

Summary: Small- and intermediate-conductance Ca2+-activated potassium channels are activated by a Ca2+-calmodulin gating mechanism. Mutations in these channels can alter their sensitivity to Ca2+, and different subtypes of channels may respond differently to mutations. Negative gating modulators could potentially be used as therapeutics.

CELL CALCIUM (2022)

Article Physiology

Hydrophobic interactions between the HA helix and S4-S5 linker modulate apparent Ca2+ sensitivity of SK2 channels

Young-Woo Nam et al.

Summary: The hydrophobic interactions between the HA helix and the S4-S5 linker are found to be the main determinant of channel apparent Ca(2+) sensitivity in SK2 channels. Mutations that alter the hydrophobicity at this interface can lead to either hypersensitivity or hyposensitivity to Ca2+. This study highlights the crucial role of interactions between the HA helix and S4-S5 linker in regulating the Ca(2+) sensitivity of SK2 channels.

ACTA PHYSIOLOGICA (2021)

Article Dentistry, Oral Surgery & Medicine

Activated KCNQ1 channel promotes fibrogenic response in hereditary gingival fibromatosis via clustering and activation of Ras

Qian Gao et al.

Summary: The study explores the pathogenic role of aberrantly activated KCNQ1 potassium channel in Hereditary Gingival Fibromatosis (HGF). Results show that upregulated KCNQ1 in gingival tissues derived from HGF patients and HGF gingival fibroblasts presented increased outward K+ currents, promoting fibrotic responses in NHGFs via the Ras/MAPK/AP-1 signaling pathway.

JOURNAL OF PERIODONTAL RESEARCH (2021)

Article Biochemistry & Molecular Biology

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

Karen W. Gripp et al.

Summary: Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function variants in corresponding genes can lead to a spectrum of human disorders. Syndromic developmental disorders such as Zimmermann-Laband, Temple-Baraitser, and FHEIG syndromes have recently been associated with GOF missense variants in potassium channel encoding genes. There is notable overlap in the phenotypic findings of these syndromes, suggesting a new subgroup of potassium channelopathies.

EUROPEAN JOURNAL OF HUMAN GENETICS (2021)

Review Physiology

Cardiac small-conductance calcium-activated potassium channels in health and disease

Xiao-Dong Zhang et al.

Summary: SK channels, encoded by KCNN genes, play critical roles in regulating cardiac excitability. They are primarily expressed in atrial myocytes and pacemaking cells, and are upregulated in ventricular myocytes in heart failure and pulmonary veins in atrial fibrillation models. Studies suggest potential therapeutic implications of SK channels in atrial arrhythmias.

PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY (2021)

Letter Hematology

Multiple thrombosis in a patient with Gardos channelopathy and a new KCNN4 mutation

Lamisse Mansour-Hendili et al.

AMERICAN JOURNAL OF HEMATOLOGY (2021)

Review Hematology

Recent advances in the pathophysiology of PIEZO1-related hereditary xerocytosis

Nicolas Jankovsky et al.

Summary: Hereditary xerocytosis is a rare red blood cell disease caused by gain-of-function mutations in the FAM38A gene, affecting PIEZO1. PIEZO1 plays a crucial role in adapting intracellular ionic content and cell hydration to mechanical stress, with recent studies revealing additional roles in erythropoiesis and other tissues.

AMERICAN JOURNAL OF HEMATOLOGY (2021)

Review Pharmacology & Pharmacy

Pharmacology of Small- and Intermediate-Conductance Calcium-Activated Potassium Channels

Brandon M. Brown et al.

ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, VOL 60 (2020)

Article Clinical Neurology

KCNN2 mutation in autosomal-dominant tremulous myoclonus-dystonia

B. Balint et al.

EUROPEAN JOURNAL OF NEUROLOGY (2020)

Article Neurosciences

Ataxic Symptoms in Huntington's Disease Transgenic Mouse Model Are Alleviated by Chlorzoxazone

Polina A. Egorova et al.

FRONTIERS IN NEUROSCIENCE (2020)

Article Multidisciplinary Sciences

The once and future gene therapy

Karen Bulaklak et al.

NATURE COMMUNICATIONS (2020)

Article Hematology

Gardos channelopathy: functional analysis of a novel KCNN4 variant

Elisa Fermo et al.

BLOOD ADVANCES (2020)

Article Genetics & Heredity

Identification of common genetic risk variants for autism spectrum disorder

Jakob Grove et al.

NATURE GENETICS (2019)

Article Clinical Neurology

Repurposing the KCa3.1 inhibitor senicapoc for Alzheimer's disease

Lee-Way Jin et al.

ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY (2019)

Article Pharmacology & Pharmacy

The Trials and Tribulations of Structure Assisted Design of KCa Channel Activators

Heesung Shim et al.

FRONTIERS IN PHARMACOLOGY (2019)

Article Genetics & Heredity

Novel Gene-Based Analysis of ASD GWAS: Insight Into the Biological Role of Associated Genes

Aitana Alonso-Gonzalez et al.

FRONTIERS IN GENETICS (2019)

Article Genetics & Heredity

Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome

Christiane K. Bauer et al.

AMERICAN JOURNAL OF HUMAN GENETICS (2018)

Article Multidisciplinary Sciences

Two missense mutations in KCNQ1 cause pituitary hormone deficiency and maternally inherited gingival fibromatosis

Johanna Tommiska et al.

NATURE COMMUNICATIONS (2017)

Article Multidisciplinary Sciences

'Gardos Channelopathy': a variant of hereditary Stomatocytosis with complex molecular regulation

Elisa Fermo et al.

SCIENTIFIC REPORTS (2017)

Article Pharmacology & Pharmacy

A new negative allosteric modulator, AP14145, for the study of small conductance calcium-activated potassium (KCa2) channels

Rafel Simo-Vicens et al.

BRITISH JOURNAL OF PHARMACOLOGY (2017)

Review Biochemistry & Molecular Biology

Functional diversity of potassium channel voltage-sensing domains

Leon D. Islas

CHANNELS (2016)

Article Gastroenterology & Hepatology

A de novo mutation in KCNN3 associated with autosomal dominant idiopathic non-cirrhotic portal hypertension

Bart G. P. Koot et al.

JOURNAL OF HEPATOLOGY (2016)

Article Neurosciences

Cellular and circuit mechanisms underlying spinocerebellar ataxias

Pratap Meera et al.

JOURNAL OF PHYSIOLOGY-LONDON (2016)

Article Hematology

Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis)

Immacolata Andolfo et al.

AMERICAN JOURNAL OF HEMATOLOGY (2015)

Article Hematology

A mutation in the Gardos channel is associated with hereditary xerocytosis

Raphael Rapetti-Mauss et al.

BLOOD (2015)

Article Genetics & Heredity

Mutations in KCNH1 and ATP6V1B2 cause Zimmermann-Laband syndrome

Fanny Kortuem et al.

NATURE GENETICS (2015)

Article Cardiac & Cardiovascular Systems

Endothelium-Dependent Hyperpolarization and Endothelial Dysfunction

Michel Félétou

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY (2015)

Article Pharmacology & Pharmacy

New Positive Ca2+-Activated K+ Channel Gating Modulators with Selectivity for KCa3.1

Nichole Coleman et al.

MOLECULAR PHARMACOLOGY (2014)

Article Neurosciences

Purkinje cell dysfunction and loss in a knock-in mouse model of Huntington Disease

S. E. Dougherty et al.

EXPERIMENTAL NEUROLOGY (2013)

Article Biochemistry & Molecular Biology

Changes in Purkinje cell firing and gene expression precede behavioral pathology in a mouse model of SCA2

Stephen T. Hansen et al.

HUMAN MOLECULAR GENETICS (2013)

Article Multidisciplinary Sciences

Overexpression of calcium-activated potassium channels underlies cortical dysfunction in a model of PTEN-associated autism

Pablo Garcia-Junco-Clemente et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Review Physiology

Small-Conductance Ca2+-Activated K+ Channels: Form and Function

John P. Adelman et al.

ANNUAL REVIEW OF PHYSIOLOGY, VOL 74 (2012)

Review Neurosciences

SK2 channel expression and function in cerebellar Purkinje cells

Eric Hosy et al.

JOURNAL OF PHYSIOLOGY-LONDON (2011)

Article Genetics & Heredity

Common variants in KCNN3 are associated with lone atrial fibrillation

Patrick T. Ellinor et al.

NATURE GENETICS (2010)

Review Biochemistry & Molecular Biology

Molecular and cellular basis of small- and intermediate-conductance, calcium-activated potassium channel function in the brain

P. Pedarzani et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2008)

Article Cardiac & Cardiovascular Systems

Functional roles of a Ca2+-activated K+ channel in atrioventricular nodes

Qian Zhang et al.

CIRCULATION RESEARCH (2008)

Article Pharmacology & Pharmacy

Selective positive modulation of the SK3 and SK2 subtypes of small conductance Ca2+-activated K+ channels

C. Hougaard et al.

BRITISH JOURNAL OF PHARMACOLOGY (2007)

Article Cardiac & Cardiovascular Systems

Differential expression of small-conductance Ca2+-activated K+ channels SK1, SK2, and SK3 in mouse atrial and ventricular myocytes

D Tuteja et al.

AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY (2005)

Article Medicine, Research & Experimental

Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia

VG Shakkottai et al.

JOURNAL OF CLINICAL INVESTIGATION (2004)

Article Biochemistry & Molecular Biology

Activation of human IK and SK Ca2+-activated K+ channels by NS309 (6,7-dichloro-1H-indole-2,3-dione 3-oxime)

D Strobæk et al.

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES (2004)

Article Biochemistry & Molecular Biology

Molecular identification and functional roles of a Ca2+-activated K+ channel in human and mouse hearts

YF Xu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2003)

Article Multidisciplinary Sciences

The hSK4 (KCNN4) isoform is the Ca2+-activated K+ channel (Gardos channel) in human red blood cells

JF Hoffman et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2003)

Article Multidisciplinary Sciences

Design of a potent and selective inhibitor of the intermediate-conductance Ca2+-activated K+ channel, IKCa1:: A potential immunosuppressant

H Wulff et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2000)