Physiology and pharmacology of two-pore domain potassium channels

Searching the DNA database has led to the identification of a class of K+ channels now referred to as two-pore or tandem-pore domain K+ (K,p) channels. The K-2P channel is structurally unique in that each subunit possesses two pore-forming domains and four transmembrane segments. In mammals, sixteen K-2P channel genes have been identified, and their mRNA transcripts are expressed in many different cell types and tissues. K-2P channels have properties of background or leak K+ channels, and therefore play a crucial role in setting the resting membrane potential and regulating cell excitability. Some K-2P channels are activated by certain physical and chemical factors such as lipids, volatile anesthetics, heat. oxygen, protons and membrane tension. Some K-2P Channels are targets of agonists that bind receptors coupled to different types of G proteins, and are probably involved in a variety of neurotransmitter and peptide hormone-mediated signal transduction processes. Such diverse properties of K-2P channels suggest that they are involved in many different physiological and pathophysiological processes. Therefore, K-2P channels could become potentially important therapeutic targets for the treatment of various pathological conditions.