Neuronal background two-P-domain potassium channels : molecular and functional aspects

Background K+ conductances are a major determinant of membrane resting potential and input resistance, two key components of neuronal excitability. Background channels have been cloned and form a K+ channel family structurally different from K-v, K-Ca and K-ir channels. These channels with 2P domains (K-2P channels) are voltage- and time-independent. They are relatively insensitive to classical potassium channels blockers such as TEA, 4-AP, Ba2+ and Cs+. TASK and TREK subunits are widely expressed in the nervous system. Open at rest, these channels mainly contribute to the resting potential of somatic motoneurons, brainstem respiratory and chemoreceptor neurones, and cerebellar granule cells. K-2P channels are regulated by numerous physical and chemical stimuli including extracellular and intracellular pH, temperature, hypoxia, pressure, bioactive lipids, and neurotransmitters. The regulation of these background K+ channels profoundly alters the neuronal excitability. For example, in Aplysia, regulation of a background potassium conductance by neurotransmitters is involved in synaptic modulation, a simple and primitive form of learning. The recent discovery that clinical compounds such as volatile anaesthetics and other neuroprotective agents including riluzole and unsaturated fatty acids activate K-2P channels suggest that neuronal background K+ channels are attractive targets for the development of new drugs.