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

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, COS Cells, Calcium-Binding Proteins, DNA, Complementary, Humans, Kv Channel-Interacting Proteins, Mice, Molecular Sequence Data, Potassium Channels, Potassium Channels, Voltage-Gated, Rats, Recombinant Proteins, Repressor Proteins, Sequence Homology, Amino Acid, Shal Potassium Channels, Two-Hybrid System Techniques, Xenopus laevis
Nature
Date: Feb. 03, 2000
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