Background: Ciglitazone, an antidiabetic agent of the thiazolidinedione family, is known to be an activator of the peroxisome-proliferator activator receptor (PPAR)-γ. The underlying mechanism of ciglitazone actions on ionic currents in neuroendocrine ceils remains unclear. Methods: The effects of ciglitazone on ionic currents were investigated in rat pituitary GH3 cells using the whole-cell and inside-out configurations of the patch-clamp technique. Results: In GH3 cells, ciglitazone at 3-300 μmol/L caused a reversible increase in the amplitude of the Ca2+-activated K+ current (I(K(Ca))) with a half-maximal concentration of 16 μmol/L. Under the inside-out patch recording mode, ciglitazone applied intracellularly increased the activity of the large-conductance Ca2+-activated K+ (BK(Ca)) channels, but did not affect their single-channel conductance. However, troglitazone (30 μmol/L) caused a reduction in the channel activity. The ciglitazone-induced ior of BK(Ca) channels is due to an increase in mean open time and a decrease in mean closed time, whereas the troglitazone-induced decrease in the channel activity is related to a decrease in mean open time and an increase in mean closed time. Ciglitazone caused a left shift in the midpoint for voltage-dependent opening. The ciglitazone-stimulated activity of BK(Ca) channels is independent of internal Ca2+. Under the current clamp mode, ciglitazone (30 μmol/L) hyperpolarized the membrane potential. Conclusions: This study shows that in addition to its activation of PPAR-γ, ciglitazone can stimulate the activity of BK(Ca) channels expressed in GH3 cells. These effects may affect membrane potentials and contribute to the ciglitazone-induced change in the functional activity of neurons or neuroendocrine cells.
|Number of pages||11|
|Journal||Journal of Investigative Medicine|
|Publication status||Published - 2000|
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)