Agonist-induced changes in Ca(2+) permeation through the nociceptor cation channel TRPA1.

Abstract:

:The Ca(2+)-permeable cation channel TRPA1 acts as an ionotropic receptor for various pungent compounds and as a noxious cold sensor in sensory neurons. It is unclear what proportion of the TRPA1-mediated current is carried by Ca(2+) ions and how the permeation pathway changes during stimulation. Here, based on the relative permeability of the nonstimulated channel to cations of different size, we estimated a pore diameter of approximately 11 A. Combined patch-clamp and Fura-2 fluorescence recordings revealed that with 2 mM extracellular Ca(2+), and at a membrane potential of -80 mV, approximately 17% of the inward TRPA1 current is carried by Ca(2+). Stimulation with mustard oil evoked an apparent dilatation of the pore of 3 A and an increase in divalent cation selectivity and fractional Ca(2+) current. Mutations in the putative pore that reduced the divalent permeability and fractional Ca(2+) current also prevented mustard-oil-induced increases in Ca(2+) permeation. It is interesting that fractional Ca(2+) currents for wild-type and mutant TRPA1 were consistently higher than values predicted based on biionic reversal potentials using the Goldman-Hodgkin-Katz equation, suggesting that binding of Ca(2+) in the pore hinders monovalent cation permeation. We conclude that the pore of TRPA1 is dynamic and supports a surprisingly large Ca(2+) influx.

journal_name

Biophys J

journal_title

Biophysical journal

authors

Karashima Y,Prenen J,Talavera K,Janssens A,Voets T,Nilius B

doi

10.1016/j.bpj.2009.11.007

subject

Has Abstract

pub_date

2010-03-03 00:00:00

pages

773-83

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(09)01731-7

journal_volume

98

pub_type

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