Enhanced activity of Ca²⁺‐activated K⁺ channels by 1‐[2‐hydroxy‐3‐propyl‐4‐[(1H‐tetrazol‐5‐yl)butoxyl]phenyl] ethanone (LY‐171883) in neuroendocrine and neuroblastoma cell lines

Abstract

The effects of LY-171883, an orally active leukotriene antagonist, on membrane currents were examined in pituitary GH(3) and in neuroblastoma IMR-32 cells. In GH(3) cells, LY-171883 (1-300 microM) reversibly increased the amplitude of Ca(2+)-activated K(+) current in a concentration-dependent manner with an EC(50) value of 15 microM. In excised inside-out patches recorded from GH(3) cells, the application of LY-171883 into cytosolic face did not modify single channel conductance of large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels; however, it did increase the channel activity. The LY-171883-stimulated activity of BK(Ca) channels is dependent on membrane potential, and results mainly from an increase in mean open time and a decrease in mean closed time. However, REV-5901 (30 microM) suppressed the activity of BK(Ca) channels and MK-571 (30 microM) did not have any effect on it. Under the current-clamp condition, LY-171883 (30 microM) caused membrane hyperpolarization as well as decreased the firing rate of action potentials in GH(3) cells. In neuroblastoma IMR-32 cells, the application of LY-171883 (30 microM) also stimulated BK(Ca) channel activity in a voltage-dependent manner. However, neither clofibrate (30 microM) nor leukotriene D(4) (10 microM) affected the channel activity in IMR-32 cells. Troglitazone (30 microM) decreased the channel activity, but ciglitazone (30 microM) enhanced it. This study clearly demonstrates that LY-171883 stimulates the activity of BK(Ca) channels in a manner unlikely to be linked to its blockade of leukotriene receptors or stimulation of peroxisome proliferator-activated receptors. The stimulatory effects on these channels may, at least in part, contribute to the underlying cellular mechanisms by which LY-171883 affects neuronal or neuroendocrine function.

Pioglitazone, a PPAR-γ Activator, Stimulates BKCa but Suppresses IKM in Hippocampal Neurons

“…Finding from the present results tends to be consistent with previous observations showing that different TZDs can regulate the activity of BK Ca channels (Wu et al, 2000; Li et al, 2002). Several studies have previously demonstrated that troglitazone and PIO might differentially perturb ionic currents in isolated cardiac myocytes and in pancreatic β cells (Ikeda and Watanabe, 1998; Sunaga et al, 1999).…”

“…They have been described to be functionally expressed in hippocampal neurons (Li et al, 2002; Huang et al, 2007; Wu et al, 2017). Another interesting paper has previously shown the function of Ca 2+ -activated K + channels in hippocampal pyramidal neurons (Storm, 1987).…”

Differential effects of quercetin, a natural polyphenolic flavonoid, on L‐Type calcium current in pituitary tumor (GH3) cells and neuronal NG108‐15 cells

“…Therefore, an additional series of current‐clamp experiments were used to determine the effect of quercetin on changes in membrane potential of GH 3 cells. When the recording pipettes were filled with K + ‐containing solution, GH 3 cells, bathed in normal Tyrode's solution containing 1.8 mM CaCl 2 , had a resting membrane potential of −57 ± 6 mV (n = 18) under this current‐clamp condition (Li et al, 2002). The typical effect of quercetin on spontaneous action potentials is illustrated in Figure 8.…”

“…The clonal rat pituitary GH 3 cells were obtained from the Culture Collection and Research Center (CCRC‐60015; Hsinchu, Taiwan). Cells were cultured in 50‐ml Ham's F‐12 medium (Life Technologies, Grand Island, NY) that was supplemented with 15% horse serum (v/v), 2.5% fetal calf serum (v/v), and 2 mM l ‐glutamate (Life Technologies) in a 5% carbon dioxide atmosphere at 37°C (Wu et al, 1998; Li et al, 2002).…”

Potassium Channel Openers: The Case of BK Channel Activators

“…(6)), chlorzoxazone [107] (Fig. (6)) and LY-1783 [108], which have been reported to possess BK-opener properties, even multiply such a chemical complexity. Ample chemical diversity is reflected in the miscellaneous pharmacological effects on BK channels and may underlie the action at different receptors in the channels and/or interaction at the same receptor but with a different set of amino acids.…”