Abstract
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 α-subunits of the Kv4, or Shal-related, channel family form A-type currents in heterologous cells3, 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 α-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 α- 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.
Original language | English (US) |
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Pages (from-to) | 553-556 |
Number of pages | 4 |
Journal | Nature |
Volume | 403 |
Issue number | 6769 |
DOIs | |
State | Published - Feb 3 2000 |
Externally published | Yes |
ASJC Scopus subject areas
- General