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
✍ Scribed by Ping-Chia Li; Jin-Tung Liang; Hung-Tu Huang; Pei-Hsuan Lin; Sheng-Nan Wu
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- English
- Weight
- 271 KB
- Volume
- 192
- Category
- Article
- ISSN
- 0021-9541
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✦ Synopsis
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 μM) reversibly increased the amplitude of Ca^2+^‐activated K^+^ current in a concentration‐dependent manner with an EC~50~ value of 15 μM. 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 μM) suppressed the activity of BK~Ca~ channels and MK‐571 (30 μM) did not have any effect on it. Under the current‐clamp condition, LY‐171883 (30 μM) 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 μM) also stimulated BK~Ca~ channel activity in a voltage‐dependent manner. However, neither clofibrate (30 μM) nor leukotriene D~4~ (10 μM) affected the channel activity in IMR‐32 cells. Troglitazone (30 μM) decreased the channel activity, but ciglitazone (30 μM) 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. © 2002 Wiley‐Liss, Inc.