The family of K2P channels: salient structural and functional properties

Abstract

Potassium channels participate in many biological functions, from ion homeostasis to generation and modulation of the electrical membrane potential. They are involved in a large variety of diseases. In the human genome, 15 genes code for K(+) channels with two pore domains (K2P ). These channels form dimers of pore-forming subunits that produce background conductances finely regulated by a range of natural and chemical effectors, including signalling lipids, temperature, pressure, pH, antidepressants and volatile anaesthetics. Since the cloning of TWIK1, the prototypical member of this family, a lot of work has been carried out on their structure and biology. These studies are still in progress, but data gathered so far show that K2P channels are central players in many processes, including ion homeostasis, hormone secretion, cell development and excitability. A growing number of studies underline their implication in physiopathological mechanisms, such as vascular and pulmonary hypertension, cardiac arrhythmias, nociception, neuroprotection and depression. This review gives a synthetic view of the most noticeable features of these channels.

Figure 1

Structural organization of K_2P channels A, schematic representation of K_2P subunit organization, with the two pore domains (in pink), the four transmembrane domains (in blue) and the extracellular cap (in green). B, three-dimensional reconstruction of TWIK1 deduced from the crystal structure (Miller & Long, ; Protein Data Bank identity code 3UKM). The different domains are represented with the same colour code as in A. C, dendrogram of the 15 K_2P subunits with their conventional and systematic names.