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Updated: Feb 6, 2026
Differentiation of the SH-SY5Y Human Neuroblastoma Cell Line
Published on: February 17, 2016
Cell Cycle Regulation by Ca2+-Activated K⁺ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells
Fatima Maqoud1, Angela Curci2, Rosa Scala3
1Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, 70125 Bari, Italy. fatima.maqoud@uniba.it.
Abstract:
The effects of Ca2+-activated K⁺ (BK) channel modulation by Paxilline (PAX) (10-7⁻10-4 M), Iberiotoxin (IbTX) (0.1⁻1 × 10-6 M) and Resveratrol (RESV) (1⁻2 × 10-4 M) on cell cycle and proliferation, AKT1pSer473 phosphorylation, cell diameter, and BK currents were investigated in SH-SY5Y cells using Operetta-high-content-Imaging-System, ELISA-assay, impedentiometric counting method and patch-clamp technique, respectively. IbTX (4 × 10-7 M), PAX (5 × 10-5 M) and RESV (10-4 M) caused a maximal decrease of the outward K⁺ current at +30 mV (Vm) of -38.3 ± 10%, -31.9 ± 9% and -43 ± 8%, respectively, which was not reversible following washout and cell depolarization. After 6h of incubation, the drugs concentration dependently reduced proliferation. A maximal reduction of cell proliferation, respectively of -60 ± 8% for RESV (2 × 10-4 M) (IC50 = 1.50 × 10-4 M), -65 ± 6% for IbTX (10-6 M) (IC50 = 5 × 10-7 M), -97 ± 6% for PAX (1 × 10-4 M) (IC50 = 1.06 × 10-5 M) and AKT1pser473 dephosphorylation was observed. PAX induced a G1/G2 accumulation and contraction of the S-phase, reducing the nuclear area and cell diameter. IbTX induced G1 contraction and G2 accumulation reducing diameter. RESV induced G2 accumulation and S contraction reducing diameter. These drugs share common actions leading to a block of the surface membrane BK channels with cell depolarization and calcium influx, AKT1pser473 dephosphorylation by calcium-dependent phosphatase, accumulation in the G2 phase, and a reduction of diameter and proliferation. In addition, the PAX action against nuclear membrane BK channels potentiates its antiproliferative effects with early apoptosis.
Insights
Paxilline, Iberiotoxin, and Resveratrol inhibit calcium-activated potassium (BK) channels, reducing cell proliferation and causing cell cycle arrest. These BK channel modulators offer potential therapeutic strategies for diseases involving cell growth.
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Calcium-activated potassium (BK) channels play crucial roles in cellular functions, including proliferation and cell cycle regulation.
- Dysregulation of BK channel activity is implicated in various pathological conditions.
Purpose of the Study:
- To investigate the effects of Paxilline (PAX), Iberiotoxin (IbTX), and Resveratrol (RESV) on BK channels in SH-SY5Y cells.
- To determine the impact of these modulators on cell proliferation, cell cycle, AKT1 phosphorylation, and cell morphology.
Main Methods:
- Utilized Operetta-high-content imaging, ELISA assays, impedentiometric counting, and patch-clamp electrophysiology.
- Investigated BK channel currents, cell proliferation, AKT1pSer473 phosphorylation, cell cycle progression, and cell diameter.
Main Results:
- PAX, IbTX, and RESV significantly reduced outward BK currents, leading to cell depolarization and calcium influx.
- All three compounds inhibited cell proliferation in a concentration-dependent manner, with significant reductions observed after 6 hours.
- PAX, IbTX, and RESV induced distinct but overlapping effects on cell cycle progression (G1, S, G2 phases) and reduced cell diameter.
- AKT1pSer473 dephosphorylation was observed, linked to calcium-dependent phosphatase activity.
- PAX exhibited potent antiproliferative effects, potentially enhanced by its action on nuclear membrane BK channels, leading to early apoptosis.
Conclusions:
- PAX, IbTX, and RESV act as BK channel blockers, inducing cell depolarization, calcium influx, AKT1pSer473 dephosphorylation, G2 cell cycle arrest, and reduced proliferation.
- These findings highlight the critical role of BK channels in regulating cell growth and suggest their potential as therapeutic targets.
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