VOLTAGE-GATED POTASSIUM (KV) CHANNELS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Voltage-gated potassium channels (http://www.ks.uiuc.edu/Research/kvchannel) are integral membrane proteins present in all three domains of life. In a specialized class of animal cells, known as excitable cells  including neurons, muscle cells, and endocrine cells  Kv channels work with other cation channels (sodium and calcium channels) to regulate the electrical activity and signaling of the cell [1]. Kv channels activate (open and close) in response to changes in the electrical potential across the cell membrane allowing passive and selective conduction of K+ ions through the channel. Potassium conduction is directed by the electrochemical gradient across the membrane and can achieve very high rates, while still discriminating against all other cations (including the smaller Na+ ions) [1]. In addition to electrical signaling in nervous systems, Kv channels play an important role in the regulation of cardiac excitability and regulation of insulin release. In humans, malfunction of these channels can result in neurological or cardiovascular diseases such as long QT syndrome or episodic ataxia [2]. The crystal structure of Kv1.2 [3], a member of the Shaker K+ channel family, has provided the first view of the molecular architecture of a mammalian potassium channel in a putative open state at 3.9 Angstrom resolution. In addition to the ion conduction pore, four voltage sensor domains are also partially identified in the structure. The voltage sensors contain several charged residues that respond to the changes in the electric field [4, 5, 6, 7],and, thus, control opening and closing of the channel.