The two-pore K-2P channel family comprises TASK, TREK, TWIK, TRESK, TALK, and THIK subfamilies, and TALK-1, TALK-2, and TASK-2 are functional members of the TALK subfamily. Here we report for the first time the single-channel properties of TALK-2 and its pH(0) sensitivity, and compare them to those of TALK-1 and TASK-2. In transfected COS-7 cells, the three TALK K-2P channels could be identified easily by their differences in single-channel conductance and gating kinetics. The single-channel conductances of TALK-1, TALk-2, and TASK-2 in symmetrical 150mM KCl were 21, 33, and 70 pS (-60mV), respectively. TALK-2 was sensitive mainly to the alkaline range (pH 7-10), whereas TALK- 1 and TASK-2 were sensitive to a wider pH,, range (6-10). The effect of pH changes was mainly on the opening frequency. Thus, members of the TALK family expressed in native tissues may be identified based on their single-channel kinetics and pH. sensitivity. (C) 2004 Elsevier Inc. All rights reserved.