Next Article in Journal
Complete Chloroplast Genome Sequence and Phylogenetic Analysis of Quercus acutissima
Next Article in Special Issue
Calcium Ion Channels: Roles in Infection and Sepsis Mechanisms of Calcium Channel Blocker Benefits in Immunocompromised Patients at Risk for Infection
Previous Article in Journal
Stress-Induced Phosphorylation of Nuclear YB-1 Depends on Nuclear Trafficking of p90 Ribosomal S6 Kinase
Previous Article in Special Issue
NR1 and NR3B Composed Intranuclear N-methyl-d-aspartate Receptor Complexes in Human Melanoma Cells
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2018, 19(8), 2442; https://doi.org/10.3390/ijms19082442

Cell Cycle Regulation by Ca2+-Activated K+ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells

1
Section of Pharmacology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, 70125 Bari, Italy
2
Section of Anatomy Pathology, Department of Pharmacy-Pharmaceutical Sciences, University of Bari, Via Orabona 4, 70125 Bari, Italy
3
Section of Anatomy Pathology, Department of Veterinary Medicine, University of Bari, Via Orabona 4, 70125 Bari, Italy
*
Author to whom correspondence should be addressed.
Received: 16 July 2018 / Revised: 2 August 2018 / Accepted: 13 August 2018 / Published: 18 August 2018
(This article belongs to the Special Issue Calcium Signaling in Human Health and Diseases)
Full-Text   |   PDF [1859 KB, uploaded 18 August 2018]   |  

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. View Full-Text
Keywords: Ca2+-activated K+(BK) channel; calcium ions; cell cycle; AKT; cell volume Ca2+-activated K+(BK) channel; calcium ions; cell cycle; AKT; cell volume
Figures

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
SciFeed

Share & Cite This Article

MDPI and ACS Style

Maqoud, F.; Curci, A.; Scala, R.; Pannunzio, A.; Campanella, F.; Coluccia, M.; Passantino, G.; Zizzo, N.; Tricarico, D. Cell Cycle Regulation by Ca2+-Activated K+ (BK) Channels Modulators in SH-SY5Y Neuroblastoma Cells. Int. J. Mol. Sci. 2018, 19, 2442.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top