Potassium Channel Related Drug Discovery Products
The diverse class of membrane proteins known as potassium channels can be found in both excitable and non-excitable cells. More than 90 genes that code for the primary subunit of potassium channels are found in the human genome. Numerous structural and functional analyses of various potassium channels have been published, and these studies have deepened our understanding of the molecular mechanisms underlying the ion selectivity, conduction, and gating of potassium channels. The potassium channel serves as a therapeutic target for many diseases due to the physiological characteristic. A subfamily or even a subtype of potassium channels that is dysfunctional may result in major disorders including Alzheimer's, Parkinson's, and other conditions. The advancement of illness research aids the creation of treatments. Through chemical synthesis, virtual screening, or a mix of both, potassium channel modulators have also been found.
Overview of Potassium Channel
The largest subfamily of the 40 genes that make up the human potassium channel family, known as voltage-gated potassium channels (Kv channels), is composed of 12 subfamilies. These family members are voltage-gated and share six TM. All mammalian Kv channels are made up of four α-subunits, each of which has six TM α-helical segments, S1 to S6, and a P-loop. These subunits are organized as homo- or hetero-tetramers circumferentially around a central pore. The pore domain (PD), which is important for potassium ion selectivity, is a tetramer comprising two membrane-spanning helixes joined together by a P-loop. A channel gate in the PD regulates ion permeability. The gate's structure is a collection of overcrossing 𝜶 helixes near the channel pore's cytoplasmic entrance.
There are eight members of this family of ion channels, which is mostly triggered by intracellular Ca2+. Some of these channels do, however, respond to intracellular Cl- and Na+. Both Ca2+ and voltage activate the Kca1 family. With the exception of Kca1, which makes a seventh pass across the membrane to exit the cell, the Kca channel -subunits have six TM segments, just like the Kv.
The ancient class of ion channels that developed in prokaryotes includes the inward-rectifying potassium channels (Kir channels) found in eukaryotes. The seven distinct families that make up the 15 known mammalian Kir channels each have unique expression patterns and functional traits. The two putative membrane-spanning domains (TM1 and TM2), an extracellular pore-forming region (H5), and the cytoplasmic amino (NH2)- and car-boxy (COOH)-terminal domains have a common theme in the fundamental architectures of Kir channels.
Four TM domains and two pores, positioned in tandem, make up K2p channels. The dimer of subunits that makes up a functioning K2p channel may heteromultimerize. Instead of a tyrosine as in one-pore K channels like Kv, many K2p channels feature a phenylalanine in the GXG motif of the selectivity filter in the second PD. There are now 16 members of the class of mammalian K2p channel subunits.
