Details

Autor(en) / Beteiligte

• Christensen, Adam P
• Akyuz, Nurunisa
• Corey, David P
• Barnes, Steven

Titel

The Outer Pore and Selectivity Filter of TRPA1

Ist Teil von

• PloS one, 2016-11, Vol.11 (11), p.e0166167-e0166167

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2016

Quelle

EZB-FREE-00999 freely available EZB journals

Beschreibungen/Notizen

• TRPA1 (transient-receptor-potential-related ion channel with ankyrin domains) is a direct receptor or indirect effector for a wide variety of nociceptive signals, and thus is a compelling target for development of analgesic pharmaceuticals such as channel blockers. Recently, the structure of TRPA1 was reported, providing insights into channel assembly and pore architecture. Here we report whole-cell and single-channel current recordings of wild-type human TRPA1 as well as TRPA1 bearing point mutations of key charged residues in the outer pore. These measurements demonstrate that the glutamate at position 920 plays an important role in collecting cations into the mouth of the pore, by changing the effective surface potential by ~16 mV, while acidic residues further out have little effect on permeation. Electrophysiology experiments also confirm that the aspartate residue at position 915 represents a constriction site of the TRPA1 pore and is critical in controlling ion permeation.