Modulation of A-type potassium channels by a family of calcium sensors

Nature. 2000 Feb 3;403(6769):553-6. doi: 10.1038/35000592.


In the brain and heart, rapidly inactivating (A-type) voltage-gated potassium (Kv) currents operate at subthreshold membrane potentials to control the excitability of neurons and cardiac myocytes. Although pore-forming alpha-subunits of the Kv4, or Shal-related, channel family form A-type currents in heterologous cells, these differ significantly from native A-type currents. Here we describe three Kv channel-interacting proteins (KChIPs) that bind to the cytoplasmic amino termini of Kv4 alpha-subunits. We find that expression of KChIP and Kv4 together reconstitutes several features of native A-type currents by modulating the density, inactivation kinetics and rate of recovery from inactivation of Kv4 channels in heterologous cells. All three KChIPs co-localize and co-immunoprecipitate with brain Kv4 alpha-subunits, and are thus integral components of native Kv4 channel complexes. The KChIPs have four EF-hand-like domains and bind calcium ions. As the activity and density of neuronal A-type currents tightly control responses to excitatory synaptic inputs, these KChIPs may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • COS Cells
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / isolation & purification
  • Calcium-Binding Proteins / metabolism*
  • DNA, Complementary
  • Humans
  • Kv Channel-Interacting Proteins
  • Mice
  • Molecular Sequence Data
  • Potassium Channels / metabolism*
  • Potassium Channels, Voltage-Gated*
  • Rats
  • Recombinant Proteins / metabolism
  • Repressor Proteins*
  • Sequence Homology, Amino Acid
  • Shal Potassium Channels
  • Two-Hybrid System Techniques
  • Xenopus laevis


  • Calcium-Binding Proteins
  • Csen protein, mouse
  • DNA, Complementary
  • KCND3 protein, human
  • KCNIP1 protein, human
  • KCNIP2 protein, human
  • KCNIP3 protein, human
  • Kcnd3 protein, mouse
  • Kcnd3 protein, rat
  • Kcnip1 protein, mouse
  • Kcnip1 protein, rat
  • Kcnip2 protein, mouse
  • Kcnip2 protein, rat
  • Kcnip3 protein, rat
  • Kv Channel-Interacting Proteins
  • Potassium Channels
  • Potassium Channels, Voltage-Gated
  • Recombinant Proteins
  • Repressor Proteins
  • Shal Potassium Channels

Associated data

  • GENBANK/AF199597
  • GENBANK/AF199598
  • GENBANK/AF199599