Ashmole, I., Vavoulis, Dimitris V., Stansfeld, P. J., Mehta, Puja R., Feng, Jianfeng, Sutcliffe, M. J. and Stanfield, Peter R. (2009) The response of the tandem pore potassium channel TASK-3 (K2P9.1) to voltage : gating at the cytoplasmic mouth. Journal of Physiology, The, Vol.587 . pp. 4769-4783. doi:10.1113/jphysiol.2009.175430 ISSN 0022-3751.

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Abstract

Although the tandem pore potassium channel TASK-3 is thought to open and shut at its
selectivity filter in response to changes of extracellular pH, it is currently unknown whether the
channel also shows gating at its inner, cytoplasmic mouth through movements of membrane
helices M2 and M4.We used two electrode voltage clamp and single channel recording to show
that TASK-3 responds to voltage in a way that reveals such gating. In wild-type channels, Popen
was very low at negative voltages, but increased with depolarisation. The effect of voltage was
relatively weak and the gating charge small, ∼0.17.Mutants A237T (in M4) and N133A (in M2)
increased Popen at a given voltage, increasing mean open time and the number of openings per
burst. In addition, the relationship between Popen andvoltagewas shifted to lesspositive voltages.
Mutation of putative hinge glycines (G117A, G231A), residues that are conserved throughout
the tandem pore channel family, reduced Popen at a given voltage, shifting the relationship
with voltage to a more positive potential range. None of these mutants substantially affected
the response of the channel to extracellular acidification. We have used the results from single
channel recording to develop a simple kinetic model to show how gating occurs through two
classes of conformation change, with two routes out of the open state, as expected if gating
occurs both at the selectivity filter and at its cytoplasmic mouth.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science, Engineering and Medicine > Science > Centre for Scientific Computing Faculty of Science, Engineering and Medicine > Science > Computer Science Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) > Biological Sciences ( -2010)
Library of Congress Subject Headings (LCSH):	Potassium channels, Cytoplasm, Acids -- Physiological effect
Journal or Publication Title:	Journal of Physiology, The
Publisher:	Wiley-Blackwell Publishing Ltd.
ISSN:	0022-3751
Official Date:	15 October 2009
Dates:	Date Event 15 October 2009 Published
Volume:	Vol.587
Page Range:	pp. 4769-4783
DOI:	10.1113/jphysiol.2009.175430
Status:	Peer Reviewed
Access rights to Published version:	Open Access (Creative Commons)
Funder:	Wellcome Trust (London, England)

Data sourced from Thomson Reuters' Web of Knowledge

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