Referenced in: none

Automatically associated channels: SK1

Title: Selectivity and interactions of Ba2+ and Cs+ with wild-type and mutant TASK1 K+ channels expressed in Xenopus oocytes.

Authors: Anthony D O'Connell, Michael J Morton, Asipu Sivaprasadarao, Malcolm Hunter

Journal, date & volume: J. Physiol. (Lond.), 2005 Feb 1 , 562, 687-96

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15611021

Abstract
The acid-sensitive K(+) channel, TASK1 is a member of the K(+)-selective tandem-pore domain (K2P) channel family. Like many of the K2P channels, TASK1 is relatively insensitive to conventional channel blockers such as Ba(2+). In this paper we report the impact of mutating the pore-neighbouring histidine residues, which are involved in pH sensing, on the sensitivity to blockade by Ba(2+) and Cs(+); additionally we compare the selectivity of these channels to extracellular K(+), Na(+) and Rb(+). H98D and H98N mutants showed reduced selectivity for K(+) over both Na(+) and Rb(+), and significant permeation of Rb(+). This enhanced permeability must reflect changes in the structure or flexibility of the selectivity filter. Blockade by Ba(2+) and Cs(+) was voltage-dependent, indicating that both ions block within the pore. In 100 mm K(+), the K(D) at 0 mV for Ba(2+) was 36 +/- 10 mm (n = 6), whilst for Cs(+) it was 20 +/- 6.0 mm (n = 5). H98D was more sensitive to Ba(2+) than the wild-type (WT); in addition, the site at which Ba(2+) appears to bind was altered (WT: delta, 0.64 +/- 0.16, n = 6; H98D: delta, 0.16 +/- 0.03, n = 5, statistically different from WT; H98N: delta, 0.58 +/- 0.09, not statistically different from WT). Thus, the pore-neighbouring residue H98 contributes not only to the pH sensitivity of TASK1, but also to the structure of the conduction pathway.