title: The neuronal Kv4 channel complex.
abstract: Kv4 channel complexes mediate the neuronal somatodendritic A-type K(+) current (I(SA)), which plays pivotal roles in dendritic signal integration. These complexes are composed of pore-forming voltage-gated alpha-subunits (Shal/Kv4) and at least two classes of auxiliary beta-subunits: KChIPs (K(+)-Channel-Interacting-Proteins) and DPLPs (Dipeptidyl-Peptidase-Like-Proteins). Here, we review our investigations of Kv4 gating mechanisms and functional remodeling by specific auxiliary beta-subunits. Namely, we have concluded that: (1) the Kv4 channel complex employs novel alternative mechanisms of closed-state inactivation; (2) the intracellular Zn(2+) site in the T1 domain undergoes a conformational change tightly coupled to voltage-dependent gating and is targeted by nitrosative modulation; and (3) discrete and specific interactions mediate the effects of KChIPs and DPLPs on activation, inactivation and permeation of Kv4 channels. These studies are shedding new light on the molecular bases of I(SA) function and regulation.
authors: Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College of Thomas Jefferson University, 1020 Locust Street, JAH 245, Philadelphia, PA 19107, USA. Manuel.Covarrubias@jefferson.edu
authors: Manuel
authors: M
authors: Covarrubias
authors: Aditya
authors: A
authors: Bhattacharji
authors: Jose A
authors: JA
authors: De Santiago-Castillo
authors: Kevin
authors: K
authors: Dougherty
authors: Yuri A
authors: YA
authors: Kaulin
authors: Thanawath Ratanadilok
authors: TR
authors: Na-Phuket
authors: Guangyu
authors: G
authors: Wang
mesh_terms: D000818:Animals; D001665:Binding Sites; D015640:Ion Channel Gating; D008958:Models, Molecular; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D011487:Protein Conformation; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051672:Shal Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015032:Zinc / Q000737:chemistry / Q000378:metabolism
chemical_list: D020033:Protein Isoforms; D021122:Protein Subunits; D051672:Shal Potassium Channels; D015032:Zinc