Abstract
The Kv2 family of voltage-gated potassium channel + subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K+ current in many mammalian central neurons. Kv2.1 exhibits robust expression across many neuron types and is unique in its conditional role in modulating intrinsic excitability through changes in its phosphorylation state, which affect Kv2.1 expression, localization, and function. Much less is known of the highly related Kv2.2 subunit, especially in forebrain neurons. Here, through combined use of cortical layer markers and transgenic mouse lines, we show that Kv2.1 and Kv2.2 are localized to functionally distinct cortical cell types. Kv2.1 expression is consistently high throughout all cortical layers, especially in layer (L) 5b pyramidal neurons, whereas Kv2.2 expression is primarily limited to neurons in L2 and L5a. In addition, L4 of primary somatosensory cortex is strikingly devoid of Kv2.2 immunolabeling. The restricted pattern of Kv2.2 expression persists in Kv2.1-KO mice, suggesting distinct cell-and layer-specific functions for these two highly related Kv2 subunits. Analyses of endogenous Kv2.2 in cortical neurons in situ and recombinant Kv2.2 expressed in heterologous cells reveal that Kv2.2 is largely refractory to stimuli that trigger robust, phosphorylationdependent changes in Kv2.1 clustering and function. Immunocytochemistry and voltage-clamp recordings from outside-out macropatches reveal distinct cellular expression patterns for Kv2.1 and Kv2.2 in intratelencephalic and pyramidal tract neurons of L5, indicating circuit-specific requirements for these Kv2 paralogs. Together, these results support distinct roles for these two Kv2 channel family members in mammalian cortex.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 14922-14942 |
| Number of pages | 21 |
| Journal | Journal of Neuroscience |
| Volume | 35 |
| Issue number | 44 |
| DOIs | |
| State | Published - Nov 4 2015 |
Fingerprint
Keywords
- Electrophysiology
- Immunohistochemistry
- Localization
- Modulation
- Neocortex
- Network
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Distinct cell-and layer-specific expression patterns and independent regulation of kv2 channel subtypes in cortical pyramidal neurons. / Bishop, Hannah I.; Guan, Dongxu; Bocksteins, Elke; Parajuli, Laxmi Kumar; Murray, Karl D; Cobb, Melanie M.; Misonou, Hiroaki; Zito, Karen; Foehring, Robert C.; Trimmer, James.
In: Journal of Neuroscience, Vol. 35, No. 44, 04.11.2015, p. 14922-14942.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distinct cell-and layer-specific expression patterns and independent regulation of kv2 channel subtypes in cortical pyramidal neurons
AU - Bishop, Hannah I.
AU - Guan, Dongxu
AU - Bocksteins, Elke
AU - Parajuli, Laxmi Kumar
AU - Murray, Karl D
AU - Cobb, Melanie M.
AU - Misonou, Hiroaki
AU - Zito, Karen
AU - Foehring, Robert C.
AU - Trimmer, James
PY - 2015/11/4
Y1 - 2015/11/4
N2 - The Kv2 family of voltage-gated potassium channel + subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K+ current in many mammalian central neurons. Kv2.1 exhibits robust expression across many neuron types and is unique in its conditional role in modulating intrinsic excitability through changes in its phosphorylation state, which affect Kv2.1 expression, localization, and function. Much less is known of the highly related Kv2.2 subunit, especially in forebrain neurons. Here, through combined use of cortical layer markers and transgenic mouse lines, we show that Kv2.1 and Kv2.2 are localized to functionally distinct cortical cell types. Kv2.1 expression is consistently high throughout all cortical layers, especially in layer (L) 5b pyramidal neurons, whereas Kv2.2 expression is primarily limited to neurons in L2 and L5a. In addition, L4 of primary somatosensory cortex is strikingly devoid of Kv2.2 immunolabeling. The restricted pattern of Kv2.2 expression persists in Kv2.1-KO mice, suggesting distinct cell-and layer-specific functions for these two highly related Kv2 subunits. Analyses of endogenous Kv2.2 in cortical neurons in situ and recombinant Kv2.2 expressed in heterologous cells reveal that Kv2.2 is largely refractory to stimuli that trigger robust, phosphorylationdependent changes in Kv2.1 clustering and function. Immunocytochemistry and voltage-clamp recordings from outside-out macropatches reveal distinct cellular expression patterns for Kv2.1 and Kv2.2 in intratelencephalic and pyramidal tract neurons of L5, indicating circuit-specific requirements for these Kv2 paralogs. Together, these results support distinct roles for these two Kv2 channel family members in mammalian cortex.
AB - The Kv2 family of voltage-gated potassium channel + subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K+ current in many mammalian central neurons. Kv2.1 exhibits robust expression across many neuron types and is unique in its conditional role in modulating intrinsic excitability through changes in its phosphorylation state, which affect Kv2.1 expression, localization, and function. Much less is known of the highly related Kv2.2 subunit, especially in forebrain neurons. Here, through combined use of cortical layer markers and transgenic mouse lines, we show that Kv2.1 and Kv2.2 are localized to functionally distinct cortical cell types. Kv2.1 expression is consistently high throughout all cortical layers, especially in layer (L) 5b pyramidal neurons, whereas Kv2.2 expression is primarily limited to neurons in L2 and L5a. In addition, L4 of primary somatosensory cortex is strikingly devoid of Kv2.2 immunolabeling. The restricted pattern of Kv2.2 expression persists in Kv2.1-KO mice, suggesting distinct cell-and layer-specific functions for these two highly related Kv2 subunits. Analyses of endogenous Kv2.2 in cortical neurons in situ and recombinant Kv2.2 expressed in heterologous cells reveal that Kv2.2 is largely refractory to stimuli that trigger robust, phosphorylationdependent changes in Kv2.1 clustering and function. Immunocytochemistry and voltage-clamp recordings from outside-out macropatches reveal distinct cellular expression patterns for Kv2.1 and Kv2.2 in intratelencephalic and pyramidal tract neurons of L5, indicating circuit-specific requirements for these Kv2 paralogs. Together, these results support distinct roles for these two Kv2 channel family members in mammalian cortex.
KW - Electrophysiology
KW - Immunohistochemistry
KW - Localization
KW - Modulation
KW - Neocortex
KW - Network
UR - http://www.scopus.com/inward/record.url?scp=84946400102&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84946400102&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1897-15.2015
DO - 10.1523/JNEUROSCI.1897-15.2015
M3 - Article
C2 - 26538660
AN - SCOPUS:84946400102
VL - 35
SP - 14922
EP - 14942
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 44
ER -