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

Nam, Young‐Woo; Downey, Myles; Rahman, Mohammad Asikur; Cui, Meng; Zhang, Miao

doi:10.1038/s41401-022-00935-1

Cited by 13 publications

(21 citation statements)

References 101 publications

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“…These subtypes are critical for regulating somatic excitability in neurons. 58,59 SK channels have been identified in RGCs and are believed to be conducive to changes in spontaneous firings by RGCs during retinal development. [60][61][62] In addition, the KCNK and KCNH gene families were also enriched under the low FSS in our RNA sequencing results.…”

Section: Discussionmentioning

confidence: 99%

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids

Gong

Zou

et al. 2023

Lab Chip

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Section: Discussionmentioning

confidence: 99%

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids

Gong

Zou

et al. 2023

Lab Chip

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“…The discovery of mutations in genes encoding K + channel subunits has provided unique insights into the pathophysiology of human disorders affecting the central nervous system, heart, kidney, and other organs [ 59 ]. Decreased or increased activity of K Ca channels caused by loss-of-function (LOF) and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human channelopathies [ 60 , 61 ]. There are no known genetic disorders associated with K Ca 2.1 channels in humans.…”

Section: Ca 2+ -Activated K Ca ...mentioning

confidence: 99%

“…While neurodevelopmental disorders such as cerebellar ataxia and tremor are associated with loss-of-function K Ca 2.2 mutations [ 59 ]. The GOF mutations of K Ca 2.3 are linked with the Zimmermann–Laband syndrome (ZLS) [ 60 , 62 , 63 , 64 ] and have also been associated with an idiopathic non-cirrhotic portal hypertension (INCPH) [ 60 , 62 , 65 ], In one study [ 66 ], CAG repeat polymorphism in KCNN3 was linked to schizophrenia. On the other hand, another study [ 67 ] found that a mutation of the K Ca 2.3 channel gene ( L283fs287X ) results in the deletion of the protein N-terminal region identified in schizophrenic patients.…”

Section: Ca 2+ -Activated K Ca ...mentioning

confidence: 99%

“…These resulting mutant K Ca 2.3 channels were found to dominantly suppress K Ca 2.3 channel currents [ 67 ] (LOF mutation). It has been reported that GOF mutations of K Ca 3.1 are linked with a subset of hereditary xerocytosis (HX) (OMIM 194380), which is an autosomal dominant congenital hemolytic anemia characterized by erythrocyte dehydration [ 60 , 68 , 69 ].…”

Section: Ca 2+ -Activated K Ca ...mentioning

confidence: 99%

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Ca2+-Sensitive Potassium Channels

Orfali

Albanyan

2023

Molecules

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The Ca2+ ion is used ubiquitously as an intracellular signaling molecule due to its high external and low internal concentration. Many Ca2+-sensing ion channel proteins have evolved to receive and propagate Ca2+ signals. Among them are the Ca2+-activated potassium channels, a large family of potassium channels activated by rises in cytosolic calcium in response to Ca2+ influx via Ca2+-permeable channels that open during the action potential or Ca2+ release from the endoplasmic reticulum. The Ca2+ sensitivity of these channels allows internal Ca2+ to regulate the electrical activity of the cell membrane. Activating these potassium channels controls many physiological processes, from the firing properties of neurons to the control of transmitter release. This review will discuss what is understood about the Ca2+ sensitivity of the two best-studied groups of Ca2+-sensitive potassium channels: large-conductance Ca2+-activated K+ channels, KCa1.1, and small/intermediate-conductance Ca2+-activated K+ channels, KCa2.x/KCa3.1.

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“…have been associated with a mutation called loss-of-function (Nam, Downey, et al, 2023). Following partial dopamine denervation, the physiological adaptation to enhanced subthalamic excitability may be mediated by the activation of K Ca 2.2 channels in the subthalamic nucleus (STN) (Zhang et al, 2021).…”

Section: Activators Inhibitorsmentioning

confidence: 99%

K_Ca2.2 (KCNN2): A physiologically and therapeutically important potassium channel

Rahman,

Orfali,

Dave

et al. 2023

J of Neuroscience Research

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One group of the K+ ion channels, the small‐conductance Ca2+‐activated potassium channels (KCa2.x, also known as SK channels family), is widely expressed in neurons as well as the heart, endothelial cells, etc. They are named small‐conductance Ca2+‐activated potassium channels (SK channels) due to their comparatively low single‐channel conductance of about ~10 pS. These channels are insensitive to changes in membrane potential and are activated solely by rises in the intracellular Ca2+. According to the phylogenic research done on the KCa2.x channels family, there are three channels' subtypes: KCa2.1, KCa2.2, and KCa2.3, which are encoded by KCNN1, KCNN2, and KCNN3 genes, respectively. The KCa2.x channels regulate neuronal excitability and responsiveness to synaptic input patterns. KCa2.x channels inhibit excitatory postsynaptic potentials (EPSPs) in neuronal dendrites and contribute to the medium afterhyperpolarization (mAHP) that follows the action potential bursts. Multiple brain regions, including the hippocampus, express the KCa2.2 channel encoded by the KCNN2 gene on chromosome 5. Of particular interest, rat cerebellar Purkinje cells express KCa2.2 channels, which are crucial for various cellular processes during development and maturation. Patients with a loss‐of‐function of KCNN2 mutations typically exhibit extrapyramidal symptoms, cerebellar ataxia, motor and language developmental delays, and intellectual disabilities. Studies have revealed that autosomal dominant neurodevelopmental movement disorders resembling rodent symptoms are caused by heterozygous loss‐of‐function mutations, which are most likely to induce KCNN2 haploinsufficiency. The KCa2.2 channel is a promising drug target for spinocerebellar ataxias (SCAs). SCAs exhibit the dysregulation of firing in cerebellar Purkinje cells which is one of the first signs of pathology. Thus, selective KCa2.2 modulators are promising potential therapeutics for SCAs.

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

Cited by 13 publications

References 101 publications

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids

Ca2+-Sensitive Potassium Channels

K_Ca2.2 (KCNN2): A physiologically and therapeutically important potassium channel

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

Cited by 13 publications

References 101 publications

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids

A controllable perfusion microfluidic chip for facilitating the development of retinal ganglion cells in human retinal organoids

Ca2+-Sensitive Potassium Channels

KCa2.2 (KCNN2): A physiologically and therapeutically important potassium channel

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Product

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K_Ca2.2 (KCNN2): A physiologically and therapeutically important potassium channel