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, AKT1p^Ser473 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 AKT1p^ser473 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, AKT1p^ser473 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.

#	Concept	H-Index	Publications	Citations
1	Dermatology	2	2	75
2	Medicine	1	1	30
3	Biomedical Engineering	1	1	45
4	Pharmacology	1	1	30

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