Voltage Gated Potassium Channel Related Drug Discovery Products
The biggest gene family of potassium (K+) channels, voltage-gated potassium (Kv) channels are important controllers of neuronal excitability. They are classified into 12 subfamilies, Kv1 through Kv12, and are encoded by 40 distinct genes in humans. Tetramers made up of four α-subunits surround an ion conduction pore in mammalian Kv channels. Six α-helical transmembrane domains (S1–S6), a membrane-reentering P loop between S5 and S6, and cytosolic N- and C-termini are all present in each α-subunit. The S1-S4 sequences are crucial for channel voltage sensing and gating, while four S5-P-S6 segments line the ion conduction pore. Creative Biolabs can offer voltage gated potassium channel related products to contribute to the success of drug discovery.
Overview of Voltage Gated Potassium Channel
In all body tissues and cells, Kv1 channels are widely expressed. The Kv1 family consists of eight members (Kv1.1 -- Kv1.8), both homo- and heteromultimers of which are possible. Since at least one Kv1.1 or Kv1.2 subunit is thought to be present in neuronal Kv1 channels, these two channels are thought to be targets for a variety of CNS illnesses. Other Kv1 family members, like Kv1.5 and Kv1.3, are located in peripheral organs like the heart, vasculature, and immune system, where they are targets for the creation of drugs to treat immunological and inflammatory illnesses, as well as cardiac arrhythmias.
Numerous different types of cells and tissues, such as neurons, vascular smooth muscle, and secretory tissues, express members of the Kv2 family (Kv2.1–Kv2.2). Through heteromultimerization with'silent' Kv5, Kv6, Kv8, and Kv9 subunits, which alter expression, inactivation, and drug sensitivity, the function of potassium channels that contain Kv2 is modified. In neurons and pancreatic cells, secretory processes have been linked to Kv2.1 potassium channels. Insulin secretion is increased when Kv2.1 is inhibited by conventional inhibitors, suggesting a potential treatment approach for type 2 diabetes mellitus.
Muscle and many brain regions, including the cerebellum, express Kv3 voltage-gated potassium channels (Kv3.1–Kv3.4). Neurons can produce short action potentials at high frequencies thanks to the special biophysical characteristics of Kv3-type potassium channels, such as quick activation and fast inactivation. Kv3.4 is one member of the Kv3 family that has drawn interest as a possible therapeutic target. Kv3.4 contributes to a fast inactivating Kv current that is expressed in both skeletal muscle and neurons when co-assembled with the auxiliary component KCNE3. Periodic paralysis in muscles is related to changes in channel function brought on by KCNE3 mutations. Kv3.4 hyperactivity in the neurological system has been linked to Alzheimer's disease-related neuronal death brought on by β-amyloid peptides.
The heart (Ito) and nervous system (IA) both include relatively quickly inactivating potassium currents that are mediated by Kv4 channels (Kv4.1–Kv4.3). Kv4 channels frequently co-assemble with auxiliary subunits and scaffolding proteins, just like other Kv channels. Kv4.3 and Kv4.2 are key players in the early stages of action potential repolarization and contribute to the atrial and ventricular Ito currents in the heart. Kv4 channels are therefore possible targets for antiarrhythmic medications.
Five members make up the Kv7 family: Kv7.1 -- Kv7.5. While Kv7.2, 7.3, and 7.5 (KCNQ2, 3, and 5) are often expressed in neural tissue as well as in several smooth and skeletal muscle types, the first family member, Kv7.1 (KCNQ1), is mostly found in peripheral tissues, most notably heart and epithelia cells. Kv7.4 is only present in the inner ear and a few specific auditory nuclei, giving it a slightly more constrained expression profile.
