Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation

Qi, Miaomiao; Qian, Lingling; Wang, Ruxing

doi:10.1016/j.hlc.2021.01.009

Cited by 5 publications

(4 citation statements)

References 88 publications

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“…Both pore blockers act from the extracellular side of the membrane [ 22 , 23 , 24 ]; thus, we added them to the extracellular medium over the course of sequential changes of bath solution during the recording. It is known that SK and IK channels are activated by cytoplasmic Ca 2+ (from about 0.1 μM or more) via a calmodulin-binding mechanism [ 25 , 26 ]. Thus, we used the intra-pipette solution containing a high concentration of intracellular free Ca 2+ (10 −6 M = 1 μM or pCa6, see Section 2 ) for reliable activation of both SK and IK currents.…”

Section: Resultsmentioning

confidence: 99%

Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells

et al. 2023

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Calcium-activated potassium channels (KCa) are important participants in calcium signaling pathways due to their ability to be activated by an increase in intracellular free calcium concentration. KCa channels are involved in the regulation of cellular processes in both normal and pathophysiological conditions, including oncotransformation. Previously, using patch-clamp, we registered the KCa currents in the plasma membrane of human chronic myeloid leukemia K562 cells, whose activity was controlled by local Ca2+ entry via mechanosensitive calcium-permeable channels. Here, we performed the molecular and functional identification of KCa channels and have uncovered their role in the proliferation, migration and invasion of K562 cells. Using a combined approach, we identified the functional activity of SK2, SK3 and IK channels in the plasma membrane of the cells. Selective SK and IK channel inhibitors, apamin and TRAM-34, respectively, reduced the proliferative, migratory and invasive capabilities of human myeloid leukemia cells. At the same time, the viability of K562 cells was not affected by KCa channel inhibitors. Ca2+ imaging showed that both SK and IK channel inhibitors affect Ca2+ entry and this could underlie the observed suppression of pathophysiological reactions of K562 cells. Our data imply that SK/IK channel inhibitors could be used to slow down the proliferation and spreading of chronic myeloid leukemia K562 cells that express functionally active KCa channels in the plasma membrane.

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Section: Resultsmentioning

confidence: 99%

Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells

et al. 2023

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“…SK channels are widely distributed in humans and animals, in central nervous system (CNS) and in peripheral tissue, among them, epithelium, smooth muscle and endothelium [39]. The aim of this study in characterize the SK channels throughout the brain.…”

Section: Expression Of Sk Channels In the Central (Cns) And Periphera...mentioning

confidence: 99%

“…The aim of this study in characterize the SK channels throughout the brain. SK1 and SK2 channels are co-expressed by the neurons of the neocortex, cerebellum, hippocampus, and brain stem, and SK3 channels are located in the midbrain and hypothalamus [39]. Stocker and Pedarzani [40] performed a study using in situ hybridization to characterize the distribution pattern of SK channels in the rat brain [40].…”

Section: Expression Of Sk Channels In the Central (Cns) And Periphera...mentioning

confidence: 99%

Presence of Small-Conductance Calcium-Activated Potassium (SK) Channels in the Central and Peripheral Nervous Systems and Their Role in Health and Disease

DosSantos¹,

Filha²,

Veríssimo³

et al. 2023

J. Integr. Neurosci.

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Potassium (K + ) channels establish and maintain the resting potential of most living cells. Their activity is predominantly regulated by the membrane voltage or the K + gradient across the cell membrane. However, many cells also express small-conductance calciumactivated potassium (SK) channels, which have the unique ability to translate changes in the level of the intracellular second messenger, Ca 2+ to changes in the membrane K + conductance and, therefore, the resting membrane potential. This article reviews the structure, presence, distribution, and function of SK channels, their pharmacological modulation, and their role in health and disease, emphasizing nociception and pain.

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“…In chronic atrial fibrillation, K Ca 2.2 and K Ca 2.3 display functional significance. Pharmacological blockage of K Ca 2.x channels may be a prospective atrial‐selective target for future antiarrhythmic medication therapy (Park et al, 2008; Qi et al, 2021).…”

Section: Kca22 Channelsmentioning

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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Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation

Cited by 5 publications

References 88 publications

Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells

Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells

Presence of Small-Conductance Calcium-Activated Potassium (SK) Channels in the Central and Peripheral Nervous Systems and Their Role in Health and Disease

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

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Modulation of SK Channels: Insight Into Therapeutics of Atrial Fibrillation

Cited by 5 publications

References 88 publications

Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells

Role of Calcium-Activated Potassium Channels in Proliferation, Migration and Invasion of Human Chronic Myeloid Leukemia K562 Cells

Presence of Small-Conductance Calcium-Activated Potassium (SK) Channels in the Central and Peripheral Nervous Systems and Their Role in Health and Disease

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

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