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2017 ; 12
(4
): e0175293
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Proton and non-proton activation of ASIC channels
#MMPMID28384246
Gautschi I
; van Bemmelen MX
; Schild L
PLoS One
2017[]; 12
(4
): e0175293
PMID28384246
show ga
The Acid-Sensing Ion Channels (ASIC) exhibit a fast desensitizing current when
activated by pH values below 7.0. By contrast, non-proton ligands are able to
trigger sustained ASIC currents at physiological pHs. To analyze the functional
basis of the ASIC desensitizing and sustained currents, we have used ASIC1a and
ASIC2a mutants with a cysteine in the pore vestibule for covalent binding of
different sulfhydryl reagents. We found that ASIC1a and ASIC2a exhibit two
distinct currents, a proton-induced desensitizing current and a sustained current
triggered by sulfhydryl reagents. These currents differ in their pH dependency,
their sensitivity to the sulfhydryl reagents, their ionic selectivity and their
relative magnitude. We propose a model for ASIC1 and ASIC2 activity where the
channels can function in two distinct modes, a desensitizing mode and a sustained
mode depending on the activating ligands. The pore vestibule of the channel
represents a functional site for binding non-proton ligands to activate ASIC1 and
ASIC2 at neutral pH and to prevent channel desensitization.