Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines

So, Edmund Cheung; Huang, Yan; Hsing, Chung-Hsi; Liao, Yu Kai; Wu, Sheng‐Nan

doi:10.1016/j.ejphar.2015.03.065

Cited by 14 publications

(10 citation statements)

References 46 publications

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“…Knockdown of IKCa1 using siRNA also significantly downregulated IKCal mRNA expression levels (Figure 6), which induced apoptosis of HeLa cells (Figure 8) and then inhibited the proliferation of HeLa cells (Figure 7). Many other reports indicated that IKCa1 channels regulated the proliferation of HeLa cells through regulating membrane potential [15,34,37,45,46]. In this study, we showed that clotrimazole and IKCa1-targeting siRNA can markedly decrease the IKCa1 channel current.…”

Section: Discussionsupporting

confidence: 63%

Intermediate-Conductance-Ca2-Activated K Channel IKCa1 Is Upregulated and Promotes Cell Proliferation in Cervical Cancer

Liu

Zhan

Nie

et al. 2017

Med Sci Monit Basic Res

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BackgroundAccumulating data point to intermediate-conductance calcium-activated potassium channel (IKCa1) as a key player in controlling cell cycle progression and proliferation of human cancer cells. However, the role that IKCa1 plays in the growth of human cervical cancer cells is largely unexplored.Material/MethodsIn this study, Western blot analysis, immunohistochemical staining, and RT-PCR were first used for IKCa1protein and gene expression assays in cervical cancer tissues and HeLa cells. Then, IKCa1 channel blocker and siRNA were employed to inhibit the functionality of IKCa1 and downregulate gene expression in HeLa cells, respectively. After these treatments, we examined the level of cell proliferation by MTT method and measured IKCa1 currents by conventional whole-cell patch clamp technique. Cell apoptosis was assessed using the Annexin V-FITC/Propidium Iodide (PI) double-staining apoptosis detection kit.ResultsWe demonstrated that IKCa1 mRNA and protein are preferentially expressed in cervical cancer tissues and HeLa cells. We also showed that the IKCa1 channel blocker, clotrimazole, and IKCa1 channel siRNA can be used to suppress cervical cancer cell proliferation and decrease IKCa1 channel current. IKCa1 downregulation by specific siRNAs induced a significant increase in the proportion of apoptotic cells in HeLa cells.ConclusionsIKCa1 is overexpressed in cervical cancer tissues, and IKCa1 upregulation in cervical cancer cell linea enhances cell proliferation, partly by reducing the proportion of apoptotic cells.

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Section: Discussionsupporting

confidence: 63%

Intermediate-Conductance-Ca2-Activated K Channel IKCa1 Is Upregulated and Promotes Cell Proliferation in Cervical Cancer

Liu

Zhan

Nie

et al. 2017

Med Sci Monit Basic Res

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“…S2). Tolbutamide and TRAM‐34 were recognised to suppress the activity of ATP‐sensitive K + ( K ATP ) and intermediate‐conductance Ca 2+ ‐activated K + (IK Ca ) channels, respectively (So, Huang, Hsing, Liao, & Wu, ; Wu, Li, & Chiang, ; Yeh et al, ). Chlorotoxin (1 μM) or α‐bunagrotoxin (1 μM) also did not produce any inhibitory effects on compound #326‐mediated stimulation of I K(Ca) (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Stimulatory actions of a novel thiourea derivative on large‐conductance, calcium‐activated potassium channels

Chern

Shen

et al. 2017

Journal Cellular Physiology

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In this study, we examine whether an anti-inflammatory thiourea derivative, compound #326, actions on ion channels. The effects of compound #326 on Ca -activated K channels were evaluated by patch-clamp recordings obtained in cell-attached, inside-out or whole-cell configuration. In pituitary GH cells, compound #326 increased the amplitude of Ca -activated K currents (I ) with an EC value of 11.6 μM, which was reversed by verruculogen, but not tolbutamide or TRAM-34. Under inside-out configuration, a bath application of compound #326 raised the probability of large-conductance Ca -activated K (BK ) channels. The activation curve of BK channels was shifted to less depolarised potential with no modification of the gating charge of the curve; consequently, the difference of free energy was reduced in the presence of this compound. Compound #326-stimulated activity of BK channels is explained by a shortening of mean closed time, despite its inability to alter single-channel conductance. Neither delayed-rectifier nor erg-mediated K currents was modified. Compound #326 decreased the peak amplitude of voltage-gated Na current with no clear change in the overall current-voltage relationship of this current. In HEK293T cells expressing α-hSlo, compound #326 enhanced BK channels effectively. Intriguingly, the inhibitory actions of compound #326 on interleukin 1β in lipopolysaccharide-activated microglia were significantly reversed by verruculogen, whereas BK channel inhibitors suppressed the expressions of inducible nitric oxide synthase. The BK channels could be an important target for compound #326 if similar in vivo results occur, and the multi-functionality of BK channels in modulating microglial immunity merit further investigation.

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“…The intermediate-conductance Ca 2+ -activated K + (IK Ca ) channels (also known as K Ca 3.1) are encoded by the KCNN4 gene and strongly associated with various cellular functions, including the reciprocal regulation of Ca 2+ influx and/or K + efflux, as well as delicate control of cell growth and migration [25][26][27][28][29][30][31]. These channels have single-channel conductance of 20-60 pS and they are sensitive to be blocked by TRAM-34 and to be stimulated by DCEBIO [28,30,31].…”

Section: Introductionmentioning

confidence: 99%

Midazolam’s Effects on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-lymphocytes

Foo

Liu

et al. 2021

IJMS

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Midazolam (MDZ) could affect lymphocyte immune functions. However, the influence of MDZ on cell’s K+ currents has never been investigated. Thus, in the present study, the effects of MDZ on Jurkat T lymphocytes were studied using the patch-clamp technique. Results showed that MDZ suppressed the amplitude of delayed-rectifier K+ current (IK(DR)) in concentration-, time-, and state-dependent manners. The IC50 for MDZ-mediated reduction of IK(DR) density was 5.87 μM. Increasing MDZ concentration raised the rate of current-density inactivation and its inhibitory action on IK(DR) density was estimated with a dissociation constant of 5.14 μM. In addition, the inactivation curve of IK(DR) associated with MDZ was shifted to a hyperpolarized potential with no change on the slope factor. MDZ-induced inhibition of IK(DR) was not reversed by flumazenil. In addition, the activity of intermediate-conductance Ca2+-activated K+ (IKCa) channels was suppressed by MDZ. Furthermore, inhibition by MDZ on both IK(DR) and IKCa-channel activity appeared to be independent from GABAA receptors and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes. In conclusion, MDZ suppressed current density of IK(DR) in concentration-, time-, and state-dependent manners in Jurkat T-lymphocytes and affected immune-regulating cytokine expression in LPS/PMA-treated human T lymphocytes.

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Arecoline inhibits intermediate-conductance calcium-activated potassium channels in human glioblastoma cell lines

Cited by 14 publications

References 46 publications

Intermediate-Conductance-Ca2-Activated K Channel IKCa1 Is Upregulated and Promotes Cell Proliferation in Cervical Cancer

Intermediate-Conductance-Ca2-Activated K Channel IKCa1 Is Upregulated and Promotes Cell Proliferation in Cervical Cancer

Stimulatory actions of a novel thiourea derivative on large‐conductance, calcium‐activated potassium channels

Midazolam’s Effects on Delayed-Rectifier K+ Current and Intermediate-Conductance Ca2+-Activated K+ Channel in Jurkat T-lymphocytes

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