Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation

被引：83

作者：

Banke, T. G. ^{[1
]}

Chaplan, S. R. ^{[1
]}

Wickenden, A. D. ^{[1
]}

机构：

[1] Johnson & Johnson Pharmaceut Res & Dev, Pain & Related Disorders, San Diego, CA USA

来源：

AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2010年 / 298卷 / 06期

关键词：

transient receptor potential channels; gap junction proteins; pannexins; sensory neurons; pain; ION-CHANNEL TRPA1; RECEPTOR; ACTIVATION; TRPV1; FLEXIBILITY; INHIBITION; NOCICEPTOR; RELEASE; PROTEIN; SENSES;

D O I：

10.1152/ajpcell.00489.2009

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Banke TG, Chaplan SR, Wickenden AD. Dynamic changes in the TRPA1 selectivity filter lead to progressive but reversible pore dilation. Am J Physiol Cell Physiol 298: C1457-C1468, 2010. First published March 24, 2010; doi:10.1152/ajpcell.00489.2009.-TRPA1 is a nonselective cation channel belonging to the transient receptor potential (TRP) family that is expressed in peripheral sensory neurons and may play important roles in pain perception and inflammation. We found that agonist stimulation of TRPA1, along with other members of the TRP family (TRPV1-4 and TRPM8), can induce the appearance of a large pore permeable to large organic cations such as Yo-Pro (YP) and N-methyl-D-glucamine, in an agonist and divalent cation-dependent manner. YP uptake was not inhibited by a panel of putative gap junction/pannexin blockers, suggesting that gap junction proteins are not required in this process. Our data suggest that changes in the TRP channel selectivity filter itself result in a progressive but reversible pore dilation process, a process that is under strong regulation by external calcium ions. Our data suggest that calcium plays a novel role in setting the amount of time TRPA1 channels spend in a dilated state providing a mechanism that may limit sensory neuron activation by painful or irritating substances.

引用

页码：C1457 / C1468

页数：12

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