Yuill, K. H., Stansfeld, P. J., Ashmole, I., Sutcliffe, M. J. and Stanfield, Peter R. (2007) The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains. Pfluegers Archiv, Vol.455 (No.2). pp. 333-348. doi:10.1007/s00424-007-0282-7 ISSN 0031-6768.

Preview

PDF WRAP_Yuill_selectivity,_voltage-dependence.pdf - Requires a PDF viewer. Download (722Kb)

Request Changes to record.

Abstract

We have investigated the contribution to ionic
selectivity of residues in the selectivity filter and pore
helices of the P1 and P2 domains in the acid sensitive
potassium channel TASK-1. We used site directed mutagenesis
and electrophysiological studies, assisted by structural
models built through computational methods. We have
measured selectivity in channels expressed in Xenopus
oocytes, using voltage clamp to measure shifts in reversal
potential and current amplitudes when Rb+ or Na+ replaced
extracellular K+. Both P1 and P2 contribute to selectivity,
and most mutations, including mutation of residues in the
triplets GYG and GFG in P1 and P2, made channels nonselective.
We interpret the effects of these—and of other
mutations—in terms of the way the pore is likely to be
stabilised structurally. We show also that residues in the
outer pore mouth contribute to selectivity in TASK-1.
Mutations resulting in loss of selectivity (e.g. I94S, G95A)
were associated with slowing of the response of channels to
depolarisation. More important physiologically, pH sensitivity
is also lost or altered by such mutations. Mutations
that retained selectivity (e.g. I94L, I94V) also retained their
response to acidification. It is likely that responses both to
voltage and pH changes involve gating at the selectivity filter.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Potassium channels, Xenopus
Journal or Publication Title:	Pfluegers Archiv
Publisher:	Springer
ISSN:	0031-6768
Official Date:	2007
Dates:	Date Event 2007 Published
Volume:	Vol.455
Number:	No.2
Page Range:	pp. 333-348
DOI:	10.1007/s00424-007-0282-7
Status:	Peer Reviewed
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Biotechnology and Biological Sciences Research Council (Great Britain) (BBSRC), Wellcome Trust (London, England), Medical Research Council (Great Britain) (MRC), Novartis (Firm)

Request changes or add full text files to a record

Repository staff actions (login required)

View Item