The role of K₂p channels in anaesthesia and sleep

Abstract

Tandem two-pore potassium channels (K2Ps) have widespread expression in the central nervous system and periphery where they contribute to background membrane conductance. Some general anaesthetics promote the opening of some of these channels, enhancing potassium currents and thus producing a reduction in neuronal excitability that contributes to the transition to unconsciousness. Similarly, these channels may be recruited during the normal sleep-wake cycle as downstream effectors of wake-promoting neurotransmitters such as noradrenaline, histamine and acetylcholine. These transmitters promote K2P channel closure and thus an increase in neuronal excitability. Our understanding of the roles of these channels in sleep and anaesthesia has been largely informed by the study of mouse K2P knockout lines and what is currently predicted by in vitro electrophysiology and channel structure and gating.

Fig. 1

Similarity between TASK-3 KO ‘sleep phenotype’ mice and how TASK-3 antagonist drugs affect the sleep-wake cycle in mice. a TASK-3 KO animals (red traces) have elevated wake in the light period with concurrent reductions in both REMS and NREMS compared to wild-type mice [67]. b Similarly, mice dosed with 100 mg/kg TASK-3 antagonist ‘compound 23’ (open circles) have elevated wake in the light period with concurrent reductions in REMS and NREMS compared to mice dosed with vehicle (closed circles) (modified from Coburn et al. [17])