Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve

Kalsi, Amanpreet S.; Greenwood, Kirsty; Wilkin, Graham P.; Butt, Arthur M.

doi:10.1111/j.0021-8782.2004.00288.x

Cited by 83 publications

(88 citation statements)

References 32 publications

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“…Very robust K ir 4.1 staining was observed in wild-type thalamus, brainstem, cerebellar molecular layer and white matter, and spinal cord gray matter (Fig. 3, hippocampus, cerebellum, and spinal cord shown), in agreement with other published studies (Poopalasundaram et al, 2000;Kalsi et al, 2004). K ir 4.1 cKO brain and spinal cord displayed complete loss of K ir 4.1 (Fig.…”

Section: Resultssupporting

confidence: 91%

Conditional Knock-Out of K_ir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

Djukic¹,

Casper²,

Philpot³

et al. 2007

J. Neurosci.

541

654

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During neuronal activity, extracellular potassium concentration ([Kϩ] out ) becomes elevated and, if uncorrected, causes neuronal depolarization, hyperexcitability, and seizures. Clearance of K ϩ from the extracellular space, termed K ϩ spatial buffering, is considered to be an important function of astrocytes. Results from a number of studies suggest that maintenance of [K ϩ ] out by astrocytes is mediated by K ϩ uptake through the inward-rectifying K ir 4.1 channels. To study the role of this channel in astrocyte physiology and neuronal excitability, we generated a conditional knock-out (cKO) of K ir 4.1 directed to astrocytes via the human glial fibrillary acidic protein promoter gfa2. K ir 4.1 cKO mice die prematurely and display severe ataxia and stress-induced seizures. Electrophysiological recordings revealed severe depolarization of both passive astrocytes and complex glia in K ir 4.1 cKO hippocampal slices. Complex cell depolarization appears to be a direct consequence of K ir 4.1 removal, whereas passive astrocyte depolarization seems to arise from an indirect developmental process. Furthermore, we observed a significant loss of complex glia, suggestive of a role for K ir 4.1 in astrocyte development. K ir 4.1 cKO passive astrocytes displayed a marked impairment of both K ϩ and glutamate uptake. Surprisingly, membrane and action potential properties of CA1 pyramidal neurons, as well as basal synaptic transmission in the CA1 stratum radiatum appeared unaffected, whereas spontaneous neuronal activity was reduced in the K ir 4.1 cKO. However, high-frequency stimulation revealed greatly elevated posttetanic potentiation and short-term potentiation in K ir 4.1 cKO hippocampus. Our findings implicate a role for glial K ir 4.1 channel subunit in the modulation of synaptic strength.

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Section: Resultssupporting

confidence: 91%

Conditional Knock-Out of K_ir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

Djukic¹,

Casper²,

Philpot³

et al. 2007

J. Neurosci.

541

654

View full text Add to dashboard Cite

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“…Because reflexive coupling should be strongly affected, these vacuoles could result from an inability to redistribute the K ϩ released through Shaker-type Kv1.1 and Kv1.2 channels into the periaxonal space Devaux et al, 2002 ]. This model is consistent with the known localization of Cx32 and Cx47 at both paranodal regions and perikarya (Menichella et al, 2003;Kamasawa et al, 2005) and Kir4.1 predominantly in oligodendrocyte perikarya and astrocyte end feet (Kalsi et al, 2004).…”

Section: Kir41 ϩ/ϫsupporting

confidence: 90%

“…In support of this hypothesis, there is a striking similarity in the phenotypes of the Cx32/Cx47 dKO and the knock-out of Kir4.1, an inwardly rectifying K ϩ channel (Neusch et al, 2001). Kir4.1 is highly enriched at the perivascular end feet of astrocytes (Kalsi et al, 2004) and is known to be an important contributor to K ϩ homeostasis in the CNS (for review, see Neusch et al, 2003). Both Cx32/Cx47 and Kir4.1 KOs display a characteristic vacuolation of myelin not associated with mutations in other murine myelin genes.…”

Section: Introductionmentioning

confidence: 92%

Genetic and Physiological Evidence That Oligodendrocyte Gap Junctions Contribute to Spatial Buffering of Potassium Released during Neuronal Activity

Menichella¹,

Majdan²,

Awatramani³

et al. 2006

J. Neurosci.

160

168

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Mice lacking the K ϩ channel Kir4.1 or both connexin32 (Cx32) and Cx47 exhibit myelin-associated vacuoles, raising the possibility that oligodendrocytes, and the connexins they express, contribute to recycling the K ϩ evolved during neuronal activity. To study this possibility, we first examined the effect of neuronal activity on the appearance of vacuoles in mice lacking both Cx32 and Cx47. The size and number of myelin vacuoles was dramatically increased when axonal activity was increased, by either a natural stimulus (eye opening) or pharmacological treatment. Conversely, myelin vacuoles were dramatically reduced when axonal activity was suppressed. Second, we used genetic complementation to test for a relationship between the function of Kir4.1 and oligodendrocyte connexins. In a Cx32-null background, haploinsufficiency of either Cx47 or Kir4.1 did not affect myelin, but double heterozygotes developed vacuoles, consistent with the idea that oligodendrocyte connexins and Kir4.1 function in a common pathway. Together, these results implicate oligodendrocytes and their connexins as having critical roles in the buffering of K ϩ released during neuronal activity.

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“…[11][12][13] The proper buffering and siphoning of extracellular potassium levels by the glia cells is instrumental for providing an electrochemical gradient for driving potassium into glia and thus regaining the propagation of neuronal action potential between the nodes of Ranvier. 14 Therefore, dysfunction of Kirs may lead to cell death and structure lesions in the CNS.…”

Section: Discussionmentioning

confidence: 99%

A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen–Tawil syndrome

Chan

Chen

et al. 2010

J Hum Genet

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Andersen-Tawil syndrome (ATS) is a rare familial potassium channelopathy characterized by the clinical triad of periodic paralysis, cardiac arrhythmia and dysmorphic facial/skeletal features. The majority of ATS patients are caused by mutations of the KCNJ2 gene, which encodes the inward-rectifying potassium channel protein Kir2.1. However, the effects of the KCNJ2 mutation on the central nervous system are rarely studied. In this report, we describe a heterozygous missense mutation (p.Thr192Ile) in the KCNJ2 gene, which segregates with the disease phenotype in an ATS family. It is noted that in addition to the classical clinical phenotypes of ATS, the index patient exhibited major depression and pyramidal tract signs with diffuse periventricular white matter lesions without contrast enhancement. This mutation and the unusual clinical manifestations observed underscore the phenotypic complexity underlying ATS. Our observations expand the current knowledge of the phenotypic variability of ATS caused by the KCNJ2 mutation. Patients with ATS, especially those carrying the KCNJ2 mutations, should be monitored for their potential neuropsychiatric system involvement.

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Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve

Abstract: Deletion studies in transgenic mice indicate that the potassium inward rectifying channel Kir4.1 is crucial for oligodendrocyte differentiation and has a special role in regulation of extracellular potassium (

Cited by 83 publications

References 32 publications

Conditional Knock-Out of K_ir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

Conditional Knock-Out of K_ir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

Genetic and Physiological Evidence That Oligodendrocyte Gap Junctions Contribute to Spatial Buffering of Potassium Released during Neuronal Activity

A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen–Tawil syndrome

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Kir4.1 expression by astrocytes and oligodendrocytes in CNS white matter: a developmental study in the rat optic nerve

Abstract: Deletion studies in transgenic mice indicate that the potassium inward rectifying channel Kir4.1 is crucial for oligodendrocyte differentiation and has a special role in regulation of extracellular potassium (

Cited by 83 publications

References 32 publications

Conditional Knock-Out of Kir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

Conditional Knock-Out of Kir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

Genetic and Physiological Evidence That Oligodendrocyte Gap Junctions Contribute to Spatial Buffering of Potassium Released during Neuronal Activity

A novel neuropsychiatric phenotype of KCNJ2 mutation in one Taiwanese family with Andersen–Tawil syndrome

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Conditional Knock-Out of K_ir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation

Conditional Knock-Out of K_ir4.1 Leads to Glial Membrane Depolarization, Inhibition of Potassium and Glutamate Uptake, and Enhanced Short-Term Synaptic Potentiation