THIK-1 (K2P13.1) is a small-conductance background K+ channel in rat trigeminal ganglion neurons

Abstract

The goal of this study was to determine the molecular identity of a small conductance (~5-pS) background K+ channel expressed in trigeminal ganglion neurons. We tested the hypothesis that the 5-pS channel is a K2P channel by comparing the pharmacological and single-channel properties of THIK-1 expressed in HEK293 cells. As reported earlier, whole-cell THIK-1 current was inhibited by halothane and activated by arachidonic acid. Among 25 additional modulators tested, bupivacaine (100 μM), quinidine (50 μM) and Ba2+ (3 mM) and cold (10°C) were most effective inhibitors of THIK-1 current (>50% inhibition). In cell-attached patches with high KCl in the pipette and bath solutions, THIK-1 produced a small conductance (~5-pS) channel with a weak inwardly rectifying current-voltage relationship. Halothane, bupivacaine and cold inhibited the single-channel activities of both THIK-1 and the 5-pS channel in TG neurons, whereas arachidonic acid augmented them. THIK-1 expressed in HEK293 cells and the 5-pS channels in TG neurons were insensitive to hypoxia. Reverse transcriptase-PCR, western blot and immunocytochemical analyses suggested that THIK-1 mRNA and protein were expressed in TG neurons. These results show that THIK-1 is functionally expressed in TG neurons and contributes to the background K+ conductance.

Tandem Pore Domain Halothane-inhibited K+ Channel Subunits THIK1 and THIK2 Assemble and Form Active Channels

“…The current-voltage relationship was plotted using the mean amplitude values at different potentials. In agreement with an earlier study (34), cells transfected with THIK-1 showed short and spiky channel opening and a weak inward rectification. The unitary conductance was ϳ5 pS.…”

“…Single-channel Properties of THIK Channels-A recent study has shown that THIK1 has a very small single-channel conductance (ϳ5 pS at ϩ100 mV) and short open time duration (Ͻ0.5 ms) (34). Thus, THIK1 was the K 2P channel with the smallest unitary conductance reported so far.…”

Verapamil Inhibits TRESK (K2P18.1) Current in Trigeminal Ganglion Neurons Independently of the Blockade of Ca2+ Influx

“…The percentage of inhibition by verapamil was constant in the absence and presence of K + channel blockers (TAC; combination of tetraethyl ammonium (TEA), 4-AP, and CsCl), which do not affect the TRESK channels ( Figure 4 D; TAC to TAC + Verapamil). Figure 4 D showed whole-cell currents with spontaneous depolarizations in response to ramp voltage pulses in agreement with a previous study performed in TG neurons [ 22 ]. The whole-cell currents were reduced by TAC, and TAC-inhibited currents were reduced by verapamil treatment.…”

Adenosine A1 receptor activates background potassium channels and modulates information processing in olfactory bulb mitral cells

“…Bupivacaine inhibits THIK‐1 (Kang et al . ); however, the pharmacology of K2P channels is still poorly understood and the action of bupivacaine alone does not allow for a definite identification of the K2P channel activated by adenosine (Lesage, ). For instance, in our experiments barium did not block the adenosine‐evoked hyperpolarization, while in Purkinje neurons a THIK‐1‐like current was reduced by barium (Bushell et al .…”