The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function.

Clarke, Catherine E. and Veale, Emma L. and Wyse, Ken and Vandenberg, Jamie I. and Mathie, Alistair (2008) The M1P1 loop of TASK3 K2P channels apposes the selectivity filter and influences channel function. Journal of Biological Chemistry, 283 (25). pp. 16985-16992. ISSN 0021-9258 . (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1074/jbc.M801368200

Abstract

Channels of the two pore domain potassium (K2P) family contain two pore domains rather than one and an unusually long pre-pore extracellular linker called the M1P1 loop. The TASK (TASK1, TASK3 and TASK5) subfamily of K2P channels are regulated by a number of different pharmacological and physiological mediators. At pH 7.4 TASK3 channels are selectively blocked by zinc in a manner that is both pHo and [K]o dependent. Mutation of both the E70 residue in the M1P1 loop and the H98 residue in the pore region abolished block, suggesting the two residues may contribute to a zinc binding site. Mutation of one E70 residue and one H98 residue to cysteine in TASK3 fixed concatamer channels gave currents that were enhanced by DTT and then potently blocked by cadmium suggesting that spontaneous disulfide bridges could be formed between these two residues. Swapping the M1P1 loops of TASK1 and TASK3 channels showed that the M1P1 loop is also involved in channel regulation by pH. Therefore the TASK3 M1P1 loop lies close to the pore, regulating TASK3 channel activity.

Item Type: Article
Subjects: Q Science > QP Physiology (Living systems)
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Alistair Mathie
Date Deposited: 10 Mar 2009 17:48
Last Modified: 11 Jun 2014 10:52
Resource URI: http://kar.kent.ac.uk/id/eprint/13190 (The current URI for this page, for reference purposes)

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