Figure 2.

ATP and ADP Gate an Anesthetic-Sensitive Tonically Active Two-Pore Domain K⁺ Channel

(A–C) Effect on the 100 μM ATP-evoked current at 0 mV, normalized to control data in the same cell, of the following agents.

(A) Blockers of voltage- and calcium-gated K⁺ channels.

(B) Blockers of two-pore domain channels (quinidine and quinine also block voltage-gated K⁺ channels, and bupivacaine, propafenone and lamotrigine also block voltage-gated Na⁺ channels, but all block two-pore K⁺ channels).

(C) Effects of gaseous anesthetics and Hg²⁺.

(D and E) Response to repeatedly puffed ATP (100 μM) during superfusion of (D) tetrapentylammonium or (E) isoflurane shows a suppression of baseline current and of the response to ATP.

(F) Voltage dependence of the baseline current suppressed by tetrapentylammonium and isoflurane.

(G) Effect of tetrapentylammonium, isoflurane, and PSB-0739 on the microglial resting potential.

(H) Mean resting potential in the agents in (G), compared with the resting potential before the drug was applied (control). The lower concentration of isoflurane (0.46 mM) is a level reached in anesthesia. (A–H) are from P12 rat.

(I–L) Values of (I) ATP-evoked current, (J) membrane potential, (K) membrane resistance, and (L) cell capacitance for microglia in P15-22 mice that are WT, heterozygote, or KO for THIK-1. Numbers of cells are on bars. Data are from hippocampal slices, and are represented as mean ± SEM. See also Figures S1, S4, and S5.