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 Ba²⁺. 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 Ba²⁺ 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. Ba²⁺ and Cs⁺ blockade was voltage-dependent, indicating that both ions block within the pore. In 100 mM K⁺, the K_D at 0 mV for Ba²⁺ was 36 ± 10 mM (n = 6), whilst for Cs⁺ it was 20 ± 6.0 mM (n = 5). H98D was more sensitive to Ba²⁺ than WT; in addition, the site at which Ba²⁺ appears to bind was altered (WT, = 0.64 ± 0.16, n = 6; H98D, = 0.16 ± 0.03, n = 5, statistically different from WT; H98N = 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.