The Neuronal Kv4 Channel Complex

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 α-subunits (Shal/Kv4) and at least two classes of auxiliary β-subunits: KChIPs ( K + - Ch annel- I nteracting- P roteins) and DPLPs ( D ipeptidyl- P eptidase- L ike- P roteins). Here, we review our investigations of Kv4 gating mechanisms and functional remodeling by specific auxiliary β-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.