J Physiol 2005 Feb 01;562Pt 3:687-96. doi: 10.1113/jphysiol.2004.079020.

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

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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.

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Species referenced: Xenopus laevis
Genes referenced: kcnk3

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