【摘 要】
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Aim Large conductance Ca2+activated potassium channel (BK), expressed in the distal nephron, mediates potassium secretion.Lossoffunction of renal BK channel is closely related with aldosteronism resul
【机 构】
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Dept of Pharmacology,School of Pharmacy,Fudan University,Pudong New District,Shanghai 201203,China;D
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Aim Large conductance Ca2+activated potassium channel (BK), expressed in the distal nephron, mediates potassium secretion.Lossoffunction of renal BK channel is closely related with aldosteronism resulting from renal potassium retention and hyperkalemia.Natural products affecting BK functions are still scarce, especially activators.Here, the pharmacological characterization of curcumin, one of the compounds isolated from the herb Curcuma longa., on BK channels have been investigated.Methods BK currents were recorded by wholecell patchclamp.mRNA expressions of BK were measured by quantitative realtime PCR.The surface and total protein expressions of BK were assessed by surface biotinylation and Western blot.Functional study was performed on aortic rings.Results Curcumin potently increased BK currents in transfected HEK293 cells as well as the current density in A7r5 cells (endogenous expressed BK (α + β1) channels) with EC50 =(6.76 ± 2.24) μmol · L1 and(7.19 ±0.07) μmol · L1 , respectively.Curcumin upregulated BK protein abundance without affecting its mRNA expression in A7r5 cells.Surface expression and halflife of BK channels were increased by curcumin in HEK293 cells, which were abolished by MG132, a proteasome inhibitor.Simultaneously, ERK 1/2 phosphorylation was also increased by curcumin.U0126, an inhibitor of ERK, attenuate the curcumininduced upregulation of BK protein level.Curcumininduced relaxation in isolated rat aortic rings was significantly attenuated by paxilline,a BK channel specific blocker.Conclusion Curcumin increased BK currents and protein abundance by inhibiting proteasomal degradation and activating ERK signaling pathway.These findings suggest that curcumin is a potential BK channel activator and provide novel insight into its complicated pharmacological effects and mechanisms.
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