Gadolinium activates and sensitizes the vanilloid receptor TRPV1 through the external protonation sites

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• 作者：Karolina Tousova ; Ladislav Vyklicky ; Klara Susankova ; Jan Benedikt and Viktorie Vlachova
• 刊名：Molecular and Cellular Neuroscience
• 出版年：2005
• 出版时间：2005
• 年：2005
• 卷：30
• 期：2
• 页码：207-217
• 全文大小：645 K

文摘

Gadolinium is a recognized blocker of many types of cation channels, including several channels of the transient receptor potential (TRP) superfamily. In this study, we demonstrate that Gd³⁺, in addition to its blocking effects, activates and potentiates the recombinant vanilloid receptor TRPV1 expressed in HEK293T cells. Whole-cell currents through TRPV1 were induced by Gd³⁺ with a half-maximal activation achieved at 72 μM at +40 mV. Gd³⁺, at concentrations up to 100 μM, lowered the threshold for heat activation and potentiated the currents induced by capsaicin (1 μM) and low extracellular pH (6). Higher concentrations of Gd³⁺ (>300 μM) blocked the TRPV1 channel. Neutralizations of the two acidic residues, Glu600 and Glu648, which are the key residues conferring the proton-sensitivity to TRPV1, resulted in a loss of Gd³⁺-induced activation and/or a reduction in its potentiating effects. A trivalent nonlanthanide, Al³⁺, that possesses much a smaller atomic mass than Gd³⁺ blocked but did not activate or sensitize the TRPV1 channel. These findings indicate that Gd³⁺ activates and potentiates the TRPV1 by neutralizing two specific proton-sensitive sites on the extracellular side of the pore-forming loop.