Modulation by clamping: Kv4 and KChIP interactions

Neurochem Res. 2008 Oct;33(10):1964-9. doi: 10.1007/s11064-008-9705-x. Epub 2008 Apr 16.

Abstract

The rapidly inactivating (A-type) potassium channels regulate membrane excitability that defines the fundamental mechanism of neuronal functions such as pain signaling. Cytosolic Kv channel-interacting proteins KChIPs that belong to neuronal calcium sensor (NCS) family of calcium binding EF-hand proteins co-assemble with Kv4 (Shal) alpha subunits to form a native complex that encodes major components of neuronal somatodendritic A-type K+ current, I(SA), in neurons and transient outward current, I(TO), in cardiac myocytes. The specific binding of auxiliary KChIPs to the Kv4 N-terminus results in modulation of gating properties, surface expression and subunit assembly of Kv4 channels. Here, I attempt to emphasize the interaction between KChIPs and Kv4 based on recent progress made in understanding the structure complex in which a single KChIP1 molecule laterally clamps two neighboring Kv4.3 N-termini in a 4:4 manner. Greater insights into molecular mechanism between KChIPs and Kv4 interaction may provide therapeutic potentials of designing compounds aimed at disrupting the protein-protein interaction for treatment of membrane excitability-related disorders.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Humans
  • Kv Channel-Interacting Proteins / physiology*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Subunits / physiology
  • Sequence Alignment
  • Shal Potassium Channels / physiology*

Substances

  • Kv Channel-Interacting Proteins
  • Protein Subunits
  • Shal Potassium Channels