Curcumin inhibits bTREK-1 K+ channels and stimulates cortisol secretion from adrenocortical cells.
Bovine adrenal zona fasciculata (AZF) cells express bTREK-1 K(+) channels that set the resting membrane potential. Inhibition of these channels by adrenocorticotropic hormone (ACTH) is coupled to membrane depolarization and cortisol secretion. Curcumin, a phytochemical with medicinal properties extracted from the spice turmeric, was found to modulate both bTREK-1 K(+) currents and cortisol secretion from AZF cells. In whole-cell patch clamp experiments, curcumin inhibited bTREK-1 with an IC(50) of 0.93muM by a mechanism that was voltage-independent. bTREK-1 inhibition by curcumin occurred through interaction with an external binding site and was independent of ATP hydrolysis. Curcumin produced a concentration-dependent increase in cortisol secretion that persisted for up to 24h. At a maximally effective concentration of 50muM, curcumin increased secretion as much as 10-fold. These results demonstrate that curcumin potently inhibits bTREK-1 K(+) channels and stimulates cortisol secretion from bovine AZF cells. The inhibition of bTREK-1 by curcumin may be linked to cortisol secretion through membrane depolarization. Since TREK-1 is widely expressed in a variety of cells, it is likely that some of the biological actions of curcumin, including its therapeutic effects, may be mediated through inhibition of these K(+) channels.
Enyeart
Judith A
JA
Department of Neuroscience, The Ohio State University, College of Medicine and Public Health, 5196 Graves Hall, 333 W.10th Avenue, Columbus, OH 43210-1239, USA. enyeart.1@osu.edu
Liu
Haiyan
H
Enyeart
John J
JJ
D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D006854:Hydrocortisone / Q000378:metabolism*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000037:antagonists & inhibitors*
D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; D003474:Curcumin; D006854:Hydrocortisone