Intracellular Binding of Terfenadine Competes with Its Access to Pancreatic ß-cell ATP-Sensitive K Channels and Human ether-à-go-go-Related Gene Channels.

Most blockers of both hERG (human ether-à-go-go-related gene) channels and pancreatic ß-cell ATP-sensitive K (K) channels access their binding sites from the cytoplasmic side of the plasma membrane. It is unknown whether binding to intracellular components competes with binding of these substances to K channels. The whole-cell configuration of the patch-clamp technique, a laser-scanning confocal microscope, and fluorescence correlation spectroscopy (FCS) were used to study hERG channels expressed in HEK (human embryonic kidney) 293 cells and K channels from the clonal insulinoma cell line RINm5F.

Thioredoxin Confers Intrinsic Resistance to Cytostatic Drugs in Human Glioma Cells.

Thioredoxin (Trx) overexpression is known to be a cause of chemotherapy resistance in various tumor entities. However, Trx effects on resistance are complex and depend strictly on tissue type. In the present study, we analyzed the impact of the Trx system on intrinsic chemoresistance of human glioblastoma multiforme (GBM) cells to cytostatic drugs.

Inhibition of the PI3K but not the MEK/ERK pathway sensitizes human glioma cells to alkylating drugs.

Background: Intrinsic chemoresistance of glioblastoma (GBM) is frequently owed to activation of the PI3K and MEK/ERK pathways. These signaling cascades are tightly interconnected however the quantitative contribution of both to intrinsic resistance is still not clear. Here, we aimed at determining the activation status of these pathways in human GBM biopsies and cells and investigating the quantitative impact of both pathways to chemoresistance.

Comparison of the effects of methadone and heroin on human ether-à-go-go-related gene channels.

Torsades de pointes (TdP) is a life-threatening form of ventricular arrhythmia that occurs under conditions of delayed cardiac repolarization indicated by prolonged QT intervals in ECG recordings. The main mechanism of QT prolongation and TdP is block of the rapid component of the cardiac delayed rectifier K(+) current (I(Kr)), which is encoded by hERG (human ether-à-go-go-related gene). The opioid agonist methadone has previously been demonstrated to inhibit hERG currents, and there are reports of serious cardiac arrhythmias and deaths from TdP and ventricular fibrillation in patients taking methadone.

Effects of fluoroquinolones on HERG channels and on pancreatic beta-cell ATP-sensitive K+ channels.

An inhibition of the cardiac rapid delayed rectifier K(+) current (I(Kr)) and of the ATP-sensitive K(+) (K(ATP)) current seems to be involved in the mechanisms of the cardiotoxic effects and the alterations in glucose homeostasis, respectively, induced by some fluoroquinolones. The aim of the present study was to compare the effects of fluoroquinolone derivatives on the pore-forming subunit of the cardiac I(Kr), which is encoded by human ether-a-go-go-related gene (HERG), and on the ATP-sensitive K(+) (K(ATP)) channel from the clonal insulinoma cell line RINm5F. Sparfloxacin blocked HERG currents half-maximally (IC(50) value) at a concentration of 33.

Fluorescence microscopy studies with a fluorescent glibenclamide derivative, a high-affinity blocker of pancreatic beta-cell ATP-sensitive K+ currents.

Hypoglycemic sulfonylureas (e.g. tolbutamide, glibenclamide) exert their stimulatory effects on pancreatic beta-cells by closure of ATP-sensitive K(+) (K(ATP)) channels.