Abstract
Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family α subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs 1-4 and Kv4 family a subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP1, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 α subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7903-7915 |
| Number of pages | 13 |
| Journal | Journal of Neuroscience |
| Volume | 24 |
| Issue number | 36 |
| DOIs | |
| State | Published - Sep 8 2004 |
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Keywords
- A current
- Alzheimer's disease
- Hippocampus
- Long-term potentiation
- Shal
- Synaptic plasticity
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
KChIPs and Kv4 α subunits as integral components of A-type potassium channels in mammalian brain. / Rhodes, Kenneth J.; Carroll, Karen I.; Sung, M. Amy; Doliveira, Lisa C.; Monaghan, Michael M.; Burke, Sharon L.; Strassle, Brian W.; Buchwalder, Lynn; Menegola, Milena; Cao, Jie; An, W. Frank; Trimmer, James.
In: Journal of Neuroscience, Vol. 24, No. 36, 08.09.2004, p. 7903-7915.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - KChIPs and Kv4 α subunits as integral components of A-type potassium channels in mammalian brain
AU - Rhodes, Kenneth J.
AU - Carroll, Karen I.
AU - Sung, M. Amy
AU - Doliveira, Lisa C.
AU - Monaghan, Michael M.
AU - Burke, Sharon L.
AU - Strassle, Brian W.
AU - Buchwalder, Lynn
AU - Menegola, Milena
AU - Cao, Jie
AU - An, W. Frank
AU - Trimmer, James
PY - 2004/9/8
Y1 - 2004/9/8
N2 - Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family α subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs 1-4 and Kv4 family a subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP1, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 α subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.
AB - Voltage-gated potassium (Kv) channels from the Kv4, or Shal-related, gene family underlie a major component of the A-type potassium current in mammalian central neurons. We recently identified a family of calcium-binding proteins, termed KChIPs (Kv channel interacting proteins), that bind to the cytoplasmic N termini of Kv4 family α subunits and modulate their surface density, inactivation kinetics, and rate of recovery from inactivation (An et al., 2000). Here, we used single and double-label immunohistochemistry, together with circumscribed lesions and coimmunoprecipitation analyses, to examine the regional and subcellular distribution of KChIPs 1-4 and Kv4 family a subunits in adult rat brain. Immunohistochemical staining using KChIP-specific monoclonal antibodies revealed that the KChIP polypeptides are concentrated in neuronal somata and dendrites where their cellular and subcellular distribution overlaps, in an isoform-specific manner, with that of Kv4.2 and Kv4.3. For example, immunoreactivity for KChIP1 and Kv4.3 is concentrated in the somata and dendrites of hippocampal, striatal, and neocortical interneurons. Immunoreactivity for KChIP1, KChIP4, and Kv4.2 is concentrated in the apical and basal dendrites of hippocampal and neocortical pyramidal cells. Double-label immunofluorescence labeling revealed that throughout the forebrain, KChIP2 and KChIP4 are frequently colocalized with Kv4.2, whereas in cortical, hippocampal, and striatal interneurons, KChIP1 is frequently colocalized with Kv4.3. Coimmunoprecipitation analyses confirmed that all KChIPs coassociate with Kv4 α subunits in brain membranes, indicating that KChIPs 1-4 are integral components of native A-type Kv channel complexes and are likely to play a major role as modulators of somatodendritic excitability.
KW - A current
KW - Alzheimer's disease
KW - Hippocampus
KW - Long-term potentiation
KW - Shal
KW - Synaptic plasticity
UR - http://www.scopus.com/inward/record.url?scp=4544345240&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4544345240&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0776-04.2004
DO - 10.1523/JNEUROSCI.0776-04.2004
M3 - Article
C2 - 15356203
AN - SCOPUS:4544345240
VL - 24
SP - 7903
EP - 7915
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 36
ER -