Potent Activation of Large-Conductance Ca2+-Activated K+ Channels by the Diphenylurea 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in Pituitary Tumor (GH3) Cells

Wu, Sheng‐Nan; Peng, Hsung; Chen, Bing-Shuo; Wang, Ya-Jean; Wu, Pei‐Yu; Lin, Ming‐Wei

doi:10.1124/mol.108.049106

Cited by 18 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The single-channel conductance of IK Ca channels in U373 cells was calculated to be 32 pS, a value similar to the prototypical IK Ca channels present in other types of cells [10,11,13,26], but apparently less than that of BK Ca channels [9,27]. Moreover, clotrimazole and TRAM-34 inhibited, but chlorzoxazone and 1-EBIO stimulated the activity of these channels in U373 cells.…”

Section: Discussionmentioning

confidence: 93%

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Yeh

Hung

et al. 2016

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

Background: Temozolomide (TMZ), an oral alkylator of the imidazotetrazine family, is used to treat glioma. Whether this drug has any ionic effects in glioma cells remains largely unclear. Methods: With the aid of patch-clamp technology, we investigated the effects of TMZ on the ionic currents in U373 glioma cells. The mRNA expression of KCNN4 (K_Ca3.1) in U373 glioma cells and TMZ's effect on K⁺ currents in these KCNN4 siRNA-transfected U373 cells were investigated. Results: In whole-cell recordings, TMZ decreased the amplitude of voltage-dependent K⁺ currents (I_K) in U373 cells. TMZ-induced I_K inhibition was reversed by ionomycin or 1-ethyl-2-benzimidazolinone (1-EBIO). In cell-attached configuration, TMZ concentration-dependently reduced the activity of intermediate-conductance Ca²⁺-activated K⁺ (IK_Ca) channels with an IC₅₀ value of 9.2 µM. Chlorzoxazone or 1-EBIO counteracted the TMZ-induced inhibition of IK_Ca channels. Although TMZ was unable to modify single-channel conductance, its inhibition of IK_Ca channels was weakly voltage-dependent and accompanied by a significant prolongation in the slow component of mean closed time. However, neitherlarge-conductance Ca²⁺-activated (BK_Ca) nor inwardly rectifying K⁺ (Kir) channels were affected by TMZ. In current-clamp mode, TMZ depolarized the cell membrane and 1-EBIO reversed TMZ-induced depolarization. TMZ had no effect on I_K in KCNN4 siRNA-transfected U373 cells. Conclusion: In addition to the DNA damage it does, its inhibitory effect on IK_Ca channels accompanied by membrane depolarization could be an important mechanism underlying TMZ-induced antineoplastic actions.

show abstract

Section: Discussionmentioning

confidence: 93%

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Yeh

Hung

et al. 2016

Cell Physiol Biochem

Self Cite

View full text Add to dashboard Cite

show abstract

“…-activated K ? channels (BK Ca channels) [40], is not able to reverse the amplitude of I MEP suppressed by CQ. Therefore, it is unlikely that CQ-mediated inhibition of I MEP is associated with the activity of BK Ca channels enriched in GH 3 cells.…”

Section: Discussionmentioning

confidence: 99%

Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation

Yeh

et al. 2011

Cell Biochem Biophys

Self Cite

View full text Add to dashboard Cite

Membrane electroporation (MEP) induces a drastic change in membrane conductance and permeability. However, the underlying mechanisms by which MEP-induced currents (I(MEP)) are generated or resealed remain unclear. In this study, we investigated how the fluctuations of I(MEP) might be elicited in different types of cells, including pituitary GH(3) cells, NG108-15 neuronal cells, and RAW 264.7 macrophages. We applied the detrended fluctuation analysis (DFA) to analyze the current signals in response to large hyperpolarizations. The DFA exponents from the current signals at 10 s preceding the start of the initial I(MEP) (I(Pre)) in GH(3) cells exhibited two components (short time lag [α(1)] and long time lag [α(2)]) with a crossover threshold of about 7 ms. The α(1) value was 0.46 ± 0.04 (n = 7), whereas the α(2) value with 0.62 ± 0.05 (n = 7) indicated the presence of long-term correlations of current signals. However, during maximal I(MEP), the slope of double logarithmic plot was linear and estimated to be 0.99 ± 0.02 (n = 8) with no clear crossover. Upon changes in membrane polarization, neither short- nor long-range correlation was altered. Chloroquine (CQ), a lysosomotropic agent, decreased the I(MEP) amplitude with an IC(50) value of 46 μM; however, it had no effects on the scaling exponents of I(Pre) or I(MEP). Although CQ or membrane polarization altered the amplitudes of I(MEP), no changes in correlation properties of this current were detected. The scaling exponents derived from I(Pre) exhibit long-range correlations in these different types of cells, indicating there is a correlated character of the electropore dynamics that may be allowed to predict the MEP process.

show abstract

“…Under our experimental conditions, the transfection of α-hSlo in HEK293T cells could result in the appearance of BK Ca channels (25). In the inside-out configuration, when ranolazine (30 μM) was applied to the intracellular side of the excised patch, BK Ca -channel activity in α-hSlo-expressing HEK293T cells was reduced (Fig.…”

Section: Inhibitory Effect Of Ranolazine On the α-Hslo Channel Expresmentioning

confidence: 98%

Effects of Ranolazine, a Novel Anti-anginal Drug, on Ion Currents and Membrane Potential in Pituitary Tumor GH3 Cells and NG108-15 Neuronal Cells

Chen

Peng

et al. 2009

J Pharmacol Sci

Self Cite

View full text Add to dashboard Cite

Abstract. Ranolazine, a piperazine derivative, is currently approved for the treatment of chronic angina. However, its ionic mechanisms in other types of cells remain unclear, although it is thought to be a selective blocker of late Na + current. This study was conducted to evaluate the possible effects of ranolazine on Na, and Ca 2+-activated K + current (I K(Ca) ) in pituitary tumor (GH 3 ) cells. Ranolazine depressed the transient and late components of I Na with different potencies. This drug exerted an inhibitory effect on I K(IR) with an IC 50 value of 0.92 μM, while it slightly inhibited I K(DR) and I K(Ca) . It shifted the steady-state activation curve of I K(IR) to more positive potentials with no change in the gating charge of the channel. Ranolazine (30 μM) also reduced the activity of large-conductance Ca 2+-activated K + channels in HEK293T cells expressing α-hSlo. Under current-clamp conditions, low concentrations (e.g., 1 μM) of ranolazine increased the firing of action potentials, while at high concentrations (≥10 μM), it diminished the firing discharge. The exposure to ranolazine also suppressed I Na and I K(IR) effectively in NG108-15 neuronal cells. Our study provides evidence that ranolazine could block multiple ion currents such as I Na and I K(IR) and suggests that these actions may contribute to some of the functional activities of neurons and endocrine or neuroendocrine cells in vivo.

show abstract

Potent Activation of Large-Conductance Ca²⁺-Activated K⁺ Channels by the Diphenylurea 1,3-Bis-[2-hydroxy-5-(trifluoromethyl)phenyl]urea (NS1643) in Pituitary Tumor (GH₃) Cells

Cited by 18 publications

References 26 publications

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Evidence for the Inhibition by Temozolomide, an Imidazotetrazine Family Alkylator, of Intermediate-Conductance Ca2+-Activated K+ Channels in Glioma Cells

Investigations into the Correlation Properties of Membrane Electroporation-Induced Inward Currents: Prediction of Pore Formation

Effects of Ranolazine, a Novel Anti-anginal Drug, on Ion Currents and Membrane Potential in Pituitary Tumor GH3 Cells and NG108-15 Neuronal Cells

Contact Info

Product

Resources

About