To date at least 15 different K2P channels have been identified in mammals, that can be broadly split into six subfamilies according to their biophysical characteristics and pharmacological properties1115171820. These include the weak inward rectifiers (TWIK-1, TWIK-2 and TWIK-3), acid sensitive rectifiers (TASK-1, TASK-3, and TASK-5), lipid sensitive mechano-gated channels (TREK-1, TREK-2 and TRAAK), halothane inhibited channels (THIK-1 and THIK-2), alkaline sensitive channels (TALK-I, TALK-2 and TASK-2) and the fatty acid inhibited calcium activated channel (TRESK). In addition to important biophysical stimuli, such as pH, temperature and mechanical pressure, K2P channels are also targets for a range of clinically important drugs including inhalational and local anaesthetics, anti-psychotics, anti-depressants and neuroprotective agents (for reviews see refs 19, 21, 22, 23, 24, 25). K2P channels are also widely modulated by G protein signalling pathways and show sensitivities to a diverse array of second messenger systems111517182627. K2P channels are therefore capable of fine-tuning levels of cellular excitability under a wide range of biochemical and physiological conditions, and can be considered as central regulators of neuronal activity. Alternate splicing28293031, alternative translation initiation32, and hetero-dimerisation of K2P channel subunits333435 further increases the level of functional complexity achievable by K2P channels.