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

W. Frank An, Mark R. Bowlby, Maria Betty, Jie Cao, Hual Ping Ling, Grace Mendoza, Joseph W. Hinson, Karen I. Mattsson, Brian W. Strassle, James Trimmer, Kenneth J. Rhodes

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797 Scopus citations

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 languageEnglish (US)
Pages (from-to)553-556
Number of pages4
JournalNature
Volume403
Issue number6769
DOIs
StatePublished - Feb 3 2000
Externally publishedYes

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    Frank An, W., Bowlby, M. R., Betty, M., Cao, J., Ling, H. P., Mendoza, G., Hinson, J. W., Mattsson, K. I., Strassle, B. W., Trimmer, J., & Rhodes, K. J. (2000). Modulation of A-type potassium channels by a family of calcium sensors. Nature, 403(6769), 553-556. https://doi.org/10.1038/35000592