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KChIP1 potassium channel antibody

RRID:AB_10673162

Antibody ID

AB_10673162

Target Antigen

KChIP1 potassium channel null

Proper Citation

(UC Davis/NIH NeuroMab Facility Cat# 75-003, RRID:AB_10673162)

Clonality

monoclonal antibody

Comments

Originating manufacturer of this product. Applications: IB, ICC, IHC, IP, WB. Validation status: IF or IB (Pass), IB in brain (Pass), IHC in brain (Pass), KO (ND).

Clone ID

K55/7

Host Organism

mouse

K+ Channel Modulatory Subunits KChIP and DPP Participate in Kv4-Mediated Mechanical Pain Control.

  • Kuo YL
  • J. Neurosci.
  • 2017 Apr 19

Literature context:


Abstract:

The K+ channel pore-forming subunit Kv4.3 is expressed in a subset of nonpeptidergic nociceptors within the dorsal root ganglion (DRG), and knockdown of Kv4.3 selectively induces mechanical hypersensitivity, a major symptom of neuropathic pain. K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 are coexpressed in Kv4.3+ DRG neurons, but whether they participate in Kv4.3-mediated pain control is unknown. Here, we show the existence of a Kv4.3/KChIP1/KChIP2/DPP10 complex (abbreviated as the Kv4 complex) in the endoplasmic reticulum and cell surface of DRG neurons. After intrathecal injection of a gene-specific antisense oligodeoxynucleotide to knock down the expression of each component in the Kv4 complex, mechanical hypersensitivity develops in the hindlimbs of rats in parallel with a reduction in all components in the lumbar DRGs. Electrophysiological data further indicate that the excitability of nonpeptidergic nociceptors is enhanced. The expression of all Kv4 complex components in DRG neurons is downregulated following spinal nerve ligation (SNL). To rescue Kv4 complex downregulation, cDNA constructs encoding Kv4.3, KChIP1, and DPP10 were transfected into the injured DRGs (defined as DRGs with injured spinal nerves) of living SNL rats. SNL-evoked mechanical hypersensitivity was attenuated, accompanied by a partial recovery of Kv4.3, KChIP1, and DPP10 surface levels in the injured DRGs. By showing an interdependent regulation among components in the Kv4 complex, this study demonstrates that K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 participate in Kv4.3-mediated mechanical pain control. Thus, these modulatory subunits could be potential drug targets for neuropathic pain.SIGNIFICANCE STATEMENT Neuropathic pain, a type of moderate to severe chronic pain resulting from nerve injury or disorder, affects 6.9%-10% of the global population. However, less than half of patients report satisfactory pain relief from current treatments. K+ channels, which act to reduce nociceptor activity, have been suggested to be novel drug targets for neuropathic pain. This study is the first to show that K+ channel modulatory subunits KChIP1, KChIP2, and DPP10 are potential drug targets for neuropathic pain because they form a channel complex with the K+ channel pore-forming subunit Kv4.3 in a subset of nociceptors to selectively inhibit mechanical hypersensitivity, a major symptom of neuropathic pain.

Coexpression of auxiliary subunits KChIP and DPPL in potassium channel Kv4-positive nociceptors and pain-modulating spinal interneurons.

  • Cheng CF
  • J. Comp. Neurol.
  • 2016 Mar 1

Literature context:


Abstract:

Subthreshold A-type K(+) currents (ISA s) have been recorded from the somata of nociceptors and spinal lamina II excitatory interneurons, which sense and modulate pain, respectively. Kv4 channels are responsible for the somatodendritic ISA s. Accumulative evidence suggests that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits and two types of auxiliary subunits: K(+) channel-interacting proteins (KChIPs) and dipeptidyl peptidase-like proteins (DPPLs). Previous reports have shown Kv4.3 in a subset of nonpeptidergic nociceptors and Kv4.2/Kv4.3 in certain spinal lamina II excitatory interneurons. However, whether and which KChIP and DPPL are coexpressed with Kv4 in these ISA -expressing pain-related neurons is unknown. In this study we mapped the protein distribution of KChIP1, KChIP2, KChIP3, DPP6, and DPP10 in adult rat dorsal root ganglion (DRG) and spinal cord by immunohistochemistry. In the DRG, we found colocalization of KChIP1, KChIP2, and DPP10 in the somatic surface and cytoplasm of Kv4.3(+) nociceptors. KChIP3 appears in most Aβ and Aδ sensory neurons as well as a small population of peptidergic nociceptors, whereas DPP6 is absent in sensory neurons. In the spinal cord, KChIP1 is coexpressed with Kv4.3 in the cell bodies of a subset of lamina II excitatory interneurons, while KChIP1, KChIP2, and DPP6 are colocalized with Kv4.2 and Kv4.3 in their dendrites. Within the dorsal horn, besides KChIP3 in the inner lamina II and lamina III, we detected DPP10 in most projection neurons, which transmit pain signal to brain. The results suggest the existence of Kv4/KChIP/DPPL ternary complexes in ISA -expressing nociceptors and pain-modulating spinal interneurons.

Funding information:
  • NINDS NIH HHS - P30NS048154(United States)
  • PHS HHS - T32 016434-33(United States)

Immunohistochemical localization of DPP10 in rat brain supports the existence of a Kv4/KChIP/DPPL ternary complex in neurons.

  • Wang WC
  • J. Comp. Neurol.
  • 2015 Mar 1

Literature context:


Abstract:

Subthreshold A-type K(+) currents (ISA s) have been recorded from the cell bodies of hippocampal and neocortical interneurons as well as neocortical pyramidal neurons. Kv4 channels are responsible for the somatodendritic ISA s. It has been proposed that neuronal Kv4 channels are ternary complexes including pore-forming Kv4 subunits, K(+) channel-interacting proteins (KChIPs), and dipeptidyl peptidase-like proteins (DPPLs). However, colocalization evidence was still lacking. The distribution of DPP10 mRNA in rodent brain has been reported but its protein localization remains unknown. In this study, we generated a DPP10 antibody to label DPP10 protein in adult rat brain by immunohistochemistry. Absent from glia, DPP10 proteins appear mainly in the cell bodies of DPP10(+) neurons, not only at the plasma membrane but also in the cytoplasm. At least 6.4% of inhibitory interneurons in the hippocampus coexpressed Kv4.3, KChIP1, and DPP10, with the highest density in the CA1 strata alveus/oriens/pyramidale and the dentate hilus. Colocalization of Kv4.3/KChIP1/DPP10 was also detected in at least 6.9% of inhibitory interneurons scattered throughout the neocortex. Both hippocampal and neocortical Kv4.3/KChIP1/DPP10(+) inhibitory interneurons expressed parvalbumin or somatostatin, but not calbindin or calretinin. Furthermore, we found colocalization of Kv4.2/Kv4.3/KChIP3/DPP10 in neocortical layer 5 pyramidal neurons and olfactory bulb mitral cells. Together, although DPP10 is also expressed in some brain neurons lacking Kv4 (such as parvalbumin- and somatostatin-positive Golgi cells in the cerebellum), colocalization of DPP10 with Kv4 and KChIP at the plasma membrane of ISA -expressing neuron somata supports the existence of Kv4/KChIP/DPPL ternary complex in vivo.

Distribution and functional expression of Kv4 family α subunits and associated KChIP β subunits in the bed nucleus of the stria terminalis.

  • Rainnie DG
  • J. Comp. Neurol.
  • 2014 Feb 15

Literature context:


Abstract:

Regulation of BNSTALG neuronal firing activity is tightly regulated by the opposing actions of the fast outward potassium current, IA , mediated by α subunits of the Kv4 family of ion channels, and the transient inward calcium current, IT . Together, these channels play a critical role in regulating the latency to action potential onset, duration, and frequency, as well as dendritic back-propagation and synaptic plasticity. Previously we have shown that Type I-III BNSTALG neurons express mRNA transcripts for each of the Kv4 α subunits. However, the biophysical properties of native IA channels are critically dependent on the formation of macromolecular complexes of Kv4 channels with a family of chaperone proteins, the potassium channel-interacting proteins (KChIP1-4). Here we used a multidisciplinary approach to investigate the expression and function of Kv4 channels and KChIPs in neurons of the rat BNSTALG . Using immunofluorescence we demonstrated the pattern of localization of Kv4.2, Kv4.3, and KChIP1-4 proteins in the BNSTALG . Moreover, our single-cell reverse-transcription polymerase chain reaction (scRT-PCR) studies revealed that mRNA transcripts for Kv4.2, Kv4.3, and all four KChIPs were differentially expressed in Type I-III BNSTALG neurons. Furthermore, immunoelectron microscopy revealed that Kv4.2 and Kv4.3 channels were primarily localized to the dendrites and spines of BNSTALG neurons, and are thus ideally situated to modulate synaptic transmission. Consistent with this observation, in vitro patch clamp recordings showed that reducing postsynaptic IA in these neurons lowered the threshold for long-term potentiation (LTP) induction. These results are discussed in relation to potential modulation of IA channels by chronic stress.

The Cav3-Kv4 complex acts as a calcium sensor to maintain inhibitory charge transfer during extracellular calcium fluctuations.

  • Anderson D
  • J. Neurosci.
  • 2013 May 1

Literature context:


Abstract:

Synaptic transmission and neuronal excitability depend on the concentration of extracellular calcium ([Ca](o)), yet repetitive synaptic input is known to decrease [Ca](o) in numerous brain regions. In the cerebellar molecular layer, synaptic input reduces [Ca](o) by up to 0.4 mm in the vicinity of stellate cell interneurons and Purkinje cell dendrites. The mechanisms used to maintain network excitability and Purkinje cell output in the face of this rapid change in calcium gradient have remained an enigma. Here we use single and dual patch recordings in an in vitro slice preparation of Sprague Dawley rats to investigate the effects of physiological decreases in [Ca](o) on the excitability of cerebellar stellate cells and their inhibitory regulation of Purkinje cells. We find that a Ca(v)3-K(v)4 ion channel complex expressed in stellate cells acts as a calcium sensor that responds to a decrease in [Ca]o by dynamically adjusting stellate cell output to maintain inhibitory charge transfer to Purkinje cells. The Ca(v)3-K(v)4 complex thus enables an adaptive regulation of inhibitory input to Purkinje cells during fluctuations in [Ca](o), providing a homeostatic control mechanism to regulate Purkinje cell excitability during repetitive afferent activity.

Funding information:
  • NCI NIH HHS - CA101936-01(United States)

Probing tissue microstructure with restriction spectrum imaging: Histological and theoretical validation.

  • White NS
  • Hum Brain Mapp
  • 2013 Feb 7

Literature context:


Abstract:

Water diffusion magnetic resonance imaging (dMRI) is a powerful tool for studying biological tissue microarchitectures in vivo. Recently, there has been increased effort to develop quantitative dMRI methods to probe both length scale and orientation information in diffusion media. Diffusion spectrum imaging (DSI) is one such approach that aims to resolve such information based on the three-dimensional diffusion propagator at each voxel. However, in practice, only the orientation component of the propagator function is preserved when deriving the orientation distribution function. Here, we demonstrate how a straightforward extension of the linear spherical deconvolution (SD) model can be used to probe tissue orientation structures over a range (or "spectrum") of length scales with minimal assumptions on the underlying microarchitecture. Using high b-value Cartesian q-space data on a rat brain tissue sample, we demonstrate how this "restriction spectrum imaging" (RSI) model allows for separating the volume fraction and orientation distribution of hindered and restricted diffusion, which we argue stems primarily from diffusion in the extraneurite and intraneurite water compartment, respectively. Moreover, we demonstrate how empirical RSI estimates of the neurite orientation distribution and volume fraction capture important additional structure not afforded by traditional DSI or fixed-scale SD-like reconstructions, particularly in gray matter. We conclude that incorporating length scale information in geometric models of diffusion offers promise for advancing state-of-the-art dMRI methods beyond white matter into gray matter structures while allowing more detailed quantitative characterization of water compartmentalization and histoarchitecture of healthy and diseased tissue.

Funding information:
  • Wellcome Trust - 1R24OD011883-01(United Kingdom)

Subcellular localization and transcription regulatory potency of KCNIP/Calsenilin/DREAM/KChIP proteins in cultured primary cortical neurons do not provide support for their role in CRE-dependent gene expression.

  • Pruunsild P
  • J. Neurochem.
  • 2012 Oct 10

Literature context:


Abstract:

KCNIP3/KChIP3 (voltage-dependent K+ channel interacting protein 3), alias Calsenilin and downstream regulatory element antagonist modulator (DREAM), is a multifunctional protein that modulates A-type potassium channels, affects processing of amyloid precursor protein and regulates transcription. KCNIP3 has been described to negatively influence the activity of CREB (cAMP/Ca(2+)-response element binding protein), an essential factor in neuronal activity-dependent gene expression regulation. However, reports on intracellular localization of KCNIP3 in neurons are diverse and necessitate additional analyses of distribution of KCNIPs in cells to clarify the potential of KCNIP3 to fulfill its functions in different cell compartments. Here, we examined localization of the entire family of highly similar KCNIP proteins in neuronal cells and show that over-expressed isoforms of KCNIP1/KChIP1, KCNIP2/KChIP2, KCNIP3/KChIP3, and KCNIP4/KChIP4 had varied, yet partially overlapping subcellular localization. In addition, although some of the over-expressed KCNIP isoforms localized to the nucleus, endogenous KCNIPs were not detected in nuclei of rat primary cortical neurons. Moreover, we analyzed the role of KCNIP proteins in cAMP/Ca(2+)-response element (CRE)-dependent transcription by luciferase reporter assay and electrophoretic mobility shift assay and report that our results do not support the role for KCNIPs, including DREAM/Calsenilin/KChIP3, in modulation of CREB-mediated transcription in neurons.

Funding information:
  • NINDS NIH HHS - R01NS023022-23(United States)

Benefits and pitfalls of secondary antibodies: why choosing the right secondary is of primary importance.

  • Manning CF
  • PLoS ONE
  • 2012 Jun 7

Literature context:


Abstract:

Simultaneous labeling of multiple targets in a single sample, or multiplexing, is a powerful approach to directly compare the amount, localization and/or molecular properties of different targets in the same sample. Here we highlight the robust reliability of the simultaneous use of multiple mouse monoclonal antibodies (mAbs) of different immunoglobulin G (IgG) subclasses in a wide variety of multiplexing applications employing anti-mouse IgG subclass-specific secondary antibodies (2°Abs). We also describe the unexpected finding that IgG subclass-specific 2°Abs are superior to general anti-mouse IgG 2 °Abs in every tested application in which mouse mAbs were used. This was due to a detection bias of general anti-mouse IgG-specific 2°Abs against mAbs of the most common mouse IgG subclass, IgG1, and to a lesser extent IgG2b mAbs. Thus, when using any of numerous mouse mAbs available through commercial and non-profit sources, for cleaner and more robust results each mAb should be detected with its respective IgG subclass-specific 2°Ab and not a general anti-mouse IgG-specific 2°Ab.

Funding information:
  • NCRR NIH HHS - P40-RR17072(United States)

Pulvinar projections to the striatum and amygdala in the tree shrew.

  • Day-Brown JD
  • Front Neuroanat
  • 2010 Dec 1

Literature context:


Abstract:

Visually guided movement is possible in the absence of conscious visual perception, a phenomenon referred to as "blindsight." Similarly, fearful images can elicit emotional responses in the absence of their conscious perception. Both capabilities are thought to be mediated by pathways from the retina through the superior colliculus (SC) and pulvinar nucleus. To define potential pathways that underlie behavioral responses to unperceived visual stimuli, we examined the projections from the pulvinar nucleus to the striatum and amygdala in the tree shrew (Tupaia belangeri), a species considered to be a prototypical primate. The tree shrew brain has a large pulvinar nucleus that contains two SC-recipient subdivisions; the dorsal (Pd) and central (Pc) pulvinar both receive topographic ("specific") projections from SC, and Pd receives an additional non-topographic ("diffuse") projection from SC (Chomsung et al., 2008). Anterograde and retrograde tract tracing revealed that both Pd and Pc project to the caudate and putamen, and Pd, but not Pc, additionally projects to the lateral amygdala. Using immunocytochemical staining for substance P (SP) and parvalbumin (PV) to reveal the patch/matrix organization of tree shrew striatum, we found that SP-rich/PV-poor patches interlock with a PV-rich/SP-poor matrix. Confocal microscopy revealed that tracer-labeled pulvino-striatal terminals preferentially innervate the matrix. Electron microscopy revealed that the postsynaptic targets of tracer-labeled pulvino-striatal and pulvino-amygdala terminals are spines, demonstrating that the pulvinar nucleus projects to the spiny output cells of the striatum matrix and the lateral amygdala, potentially relaying: (1) topographic visual information from SC to striatum to aid in guiding precise movements, and (2) non-topographic visual information from SC to the amygdala alerting the animal to potentially dangerous visual images.

Funding information:
  • PHS HHS - HHSN266200400037C(United States)

Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy.

  • Monaghan MM
  • Neuroscience
  • 2008 Oct 15

Literature context:


Abstract:

Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2-3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE.

Dendritic A-type potassium channel subunit expression in CA1 hippocampal interneurons.

  • Menegola M
  • Neuroscience
  • 2008 Jun 26

Literature context:


Abstract:

Voltage-gated potassium (Kv) channels are important and diverse determinants of neuronal excitability and exhibit specific expression patterns throughout the brain. Among Kv channels, Kv4 channels are major determinants of somatodendritic A-type current and are essential in controlling the amplitude of backpropagating action potentials (BAPs) into neuronal dendrites. BAPs have been well studied in a variety of neurons, and have been recently described in hippocampal and cortical interneurons, a heterogeneous population of GABAergic inhibitory cells that regulate activity of principal cells and neuronal networks. We used well-characterized mouse monoclonal antibodies against the Kv4.3 and potassium channel interacting protein (KChIP) 1 subunits of A-type Kv channels, and antibodies against different interneuron markers in single- and double-label immunohistochemistry experiments to analyze the expression patterns of Kv4.3 and KChIP1 in hippocampal Ammon's horn (CA1) neurons. Immunohistochemistry was performed on 40 mum rat brain sections using nickel-enhanced diaminobenzidine staining or multiple-label immunofluorescence. Our results show that Kv4.3 and KChIP1 component subunits of A-type channels are co-localized in the soma and dendrites of a large number of GABAergic hippocampal interneurons. These subunits co-localize extensively but not completely with markers defining the four major interneuron subpopulations tested (parvalbumin, calbindin, calretinin, and somatostatin). These results suggest that CA1 hippocampal interneurons can be divided in two groups according to the expression of Kv4.3/KChIP1 channel subunits. Antibodies against Kv4.3 and KChIP1 represent an important new tool for identifying a subpopulation of hippocampal interneurons with a unique dendritic A-type channel complement and ability to control BAPs.

Unanticipated region- and cell-specific downregulation of individual KChIP auxiliary subunit isotypes in Kv4.2 knock-out mouse brain.

  • Menegola M
  • J. Neurosci.
  • 2006 Nov 22

Literature context:


Abstract:

Kv4 family voltage-gated potassium channel alpha subunits and Kv channel-interacting protein (KChIP) and dipeptidyl aminopeptidase-like protein subunits comprise somatodendritic A-type channels in mammalian neurons. Recently, a mouse was generated with a targeted deletion of Kv4.2, a Kv4 alpha subunit expressed in many but not all mammalian brain neurons. Kv4.2-/- mice are grossly indistinguishable from wild-type (WT) littermates. Here we used immunohistochemistry to analyze expression of component Kv4 and KChIP subunits of A-type channels in WT and Kv4.2-/- brains. We found that the expression level, and cellular and subcellular distribution of the other prominent brain Kv4 family member Kv4.3, was indistinguishable between WT and Kv4.2-/- samples. However, we found unanticipated regional and cell-specific decreases in expression of KChIPs. The degree of altered expression of individual KChIP isoforms in different regions and neurons precisely follows the level of Kv4.2 normally found at those sites and presumably their extent of association of these KChIPs with Kv4.2. The dramatic effects of Kv4.2 deletion on KChIP expression suggest that, in addition to previously characterized effects of KChIPs on the functional properties, trafficking, and turnover rate of Kv4 channels, Kv4:KChIP association may confer reciprocal Kv4.2-dependent effects on KChIPs. The impact of Kv4.2 deletion on KChIP expression also supports the major role of KChIPs as auxiliary subunits of Kv4 channels.

Funding information:
  • NCRR NIH HHS - U54RR020839(United States)