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) |
|---|---|
| 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 |
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Cite this
Modulation of A-type potassium channels by a family of calcium sensors. / Frank An, W.; Bowlby, Mark R.; Betty, Maria; Cao, Jie; Ling, Hual Ping; Mendoza, Grace; Hinson, Joseph W.; Mattsson, Karen I.; Strassle, Brian W.; Trimmer, James; Rhodes, Kenneth J.
In: Nature, Vol. 403, No. 6769, 03.02.2000, p. 553-556.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Modulation of A-type potassium channels by a family of calcium sensors
AU - Frank An, W.
AU - Bowlby, Mark R.
AU - Betty, Maria
AU - Cao, Jie
AU - Ling, Hual Ping
AU - Mendoza, Grace
AU - Hinson, Joseph W.
AU - Mattsson, Karen I.
AU - Strassle, Brian W.
AU - Trimmer, James
AU - Rhodes, Kenneth J.
PY - 2000/2/3
Y1 - 2000/2/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0034598810&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034598810&partnerID=8YFLogxK
U2 - 10.1038/35000592
DO - 10.1038/35000592
M3 - Article
C2 - 10676964
AN - SCOPUS:0034598810
VL - 403
SP - 553
EP - 556
JO - Nature
JF - Nature
SN - 0028-0836
IS - 6769
ER -