Two-pore-domain potassium channel protein (K2P channel)

Two-pore-domain potassium channel proteins are a family of potassium-selective ion channels characterized by the presence of two pore-forming domains per subunit. Unique among potassium channels, they assemble as dimers to form a functional channel, with the four total pore domains creating the selectivity filter. They are responsible for background or leak potassium currents that help stabilize the resting membrane potential and regulate excitability in many types of cells, including neurons and cardiomyocytes. Members of this family include channels such as TWIK-1, TREK-1, TASK-1, and others. K2P channels are regulated by diverse mechanisms, including pH, mechanical stretch, lipids, temperature, and G-proteins. They are therapeutic targets for pain modulation, neuroprotection, migraine, and possibly cardiac and neurological disorders. Channelopathies involving mutations in K2P channel genes can lead to diseases such as migraine and arrhythmias. These channels are also pharmacological targets for drugs like general anesthetics and neuroprotective agents. For computational or drug discovery purposes, it is important to specify the particular member of the K2P family as each has distinct functional and pharmacological properties. The entry "Tandem pore domain potassium channel protein" is not incorrect per se, but is a family name; individual druggable entities often refer to specific members (e.g., KCNK2/TREK-1, KCNK18/TRESK).

Other names

Tandem pore domain potassium channeltwo-pore-domain potassium channelK2P channelTWIKTREKTASKTRAAKTHIKTALKTRESKKCNK1/TWIK-1KCNK2/TREK-1

Channel activation (increase potassium leak, hyperpolarize membrane, reduce neuronal excitability); Channel inhibition (decrease potassium leak, depolarize membrane, enhance excitability)