Cav1.2, Cav1.3, and Cav2.1 in the mouse hippocampus during and after pilocarpine‐induced status epilepticus

Xu, Jie; Long, Liling; Tang, Yong; Hu, Hesuan; Tang, Feng Ru

doi:10.1002/hipo.20263

Cited by 46 publications

(36 citation statements)

References 31 publications

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“…In contrast, several reports have documented the expression of L-type channels in astrocytes (Akopian et al, 1996;Barres et al, 1989;D'Ascenzo et al, 2004;de Pina-Benabou et al, 2001;MacVicar, 1984;MacVicar and Tse, 1988). Interestingly, while preparing this manuscript it was reported that the expression of Ca V 2.1 is upregulated in reactive astrocytes following the induction of status epilepticus by pilocarpine (Xu et al, 2007). This finding is in line with a possible involvement of P/Q-type channels in astrogliosis.…”

Section: Discussionsupporting

confidence: 48%

“…Reactive astrocytes show increased expression of L-type Ca 21 channels in several models of CNS trauma, such as ischemia, anoxia, kainic acid-induced epilepsy, mechanical and thermal lesions, and hipomyelination (Brown et al, 2001;Chung et al, 2001;Westenbroek et al, 1998). More recently, the upregulation of the specific calcium channel subunits Ca V 1.3 and Ca V 2.1 has been described in reactive astrocytes following pilocarpine-induced epilepsy (Xu et al, 2007). Significantly, astrogliosis can be attenuated by L-type Ca 21 channel blockers both in cultured astrocytes (Lee et al, 2000;Oh et al, 1995) and in vivo models of CNS injury (Agrawal et al, 2000;Du et al, 1999;Klepper et al, 1995).…”

Section: Introductionmentioning

confidence: 97%

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PKCε upregulates voltage‐dependent calcium channels in cultured astrocytes

Burgos

Pastor

Gonzalez

et al. 2007

Glia

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Astrocytes express voltage-gated calcium channels (VGCCs) that are upregulated in the context of the reactive astrogliosis occurring in several CNS pathologies. Moreover, the ability of selective calcium channel blockers to inhibit reactive astrogliosis has been revealed in a variety of experimental models. However, the functions and regulation of VGCC in astrocytes are still poorly understood. Interestingly, protein kinase C epsilon (PKCepsilon), one of the known regulators of VGCC in several cell types, induces in astrocytes a stellated morphology similar to that associated to gliosis. Thereby, here we explored the possible regulation of VGCC by adenovirally expressed PKCepsilon in astrocytes. We found that PKCepsilon potently increases the mRNA levels of two different calcium channel alpha(1) subunits, Ca(V)1.2 (L-type channel) and Ca(V)2.1 (P/Q-type channel). The mRNA upregulation was followed by a robust increase in the corresponding peptides. Moreover, the new calcium channels formed as a consequence of PKCepsilon activation are functional, since overexpression of constitutively-active PKCepsilon increased significantly the calcium current density in astrocytes. PKCepsilon raised currents carried by both L- and P/Q-type channels. However, the effect on the P/Q-type channel was more prominent since an increase of the relative contribution of this channel to the whole cell calcium current was observed. Finally, we found that PKCepsilon-induced stellation was significantly reduced by the specific L-type channel blocker nifedipine, indicating that calcium influx through VGCC mediates the change in astrocyte morphology induced by PKCepsilon. Therefore, here we describe a novel regulatory pathway involving VGCC that participates in PKCepsilon-dependent astrocyte activation.

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Section: Discussionsupporting

confidence: 48%

Section: Introductionmentioning

confidence: 97%

PKCε upregulates voltage‐dependent calcium channels in cultured astrocytes

Burgos

Pastor

Gonzalez

et al. 2007

Glia

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“…A subset of astrocytes in the hippocampus indeed expresses Cav1.3 (Fig. 2g) [46,59], and upregulation of Cav1.3 has been demonstrated in reactive astrocytes of the mouse hippocampus after pilocarpine-induced status epilepticus [60]. Thus, Cav1.3 may contribute to volume regulation and modulation of the activity state of astrocytes in the hippocampus and could be involved in astrogliosis in chronic neurodegenerative disorders such as Alzheimer´s disease or in acute CNS lesions such as spinal cord injury.…”

Section: Discussionmentioning

confidence: 95%

The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions

et al. 2015

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L-type voltage gated Ca(2+) channels (LTCCs) are widely expressed within different brain regions including the hippocampus. The isoforms Cav1.2 and Cav1.3 have been shown to be involved in hippocampus-dependent learning and memory, cognitive functions that require proper hippocampal neurogenesis. In vitro, functional LTCCs are expressed on neuronal progenitor cells, where they promote neuronal differentiation. Expression of LTCCs on neural stem and progenitor cells within the neurogenic regions in the adult brain in vivo has not been examined so far, and a contribution of the individual isoforms Cav1.2 and Cav1.3 to adult neurogenesis remained to be clarified. To reveal the role of these channels we first evaluated the expression patterns of Cav1.2 and Cav1.3 in the hippocampal dentate gyrus and the subventricular zone (SVZ) in adult (2- and 3-month old) and middle-aged (15-month old) mice on mRNA and protein levels. We performed immunohistological analysis of hippocampal neurogenesis in adult and middle-aged Cav1.3(-/-) mice and finally addressed the importance of Cav1.3 for hippocampal function by evaluating spatial memory and depression-like behavior in adult Cav1.3(-/-) mice. Our results showed Cav1.2 and Cav1.3 expression at different stages of neuronal differentiation. While Cav1.2 was primarily restricted to mature NeuN(+) granular neurons, Cav1.3 was expressed in Nestin(+) neural stem cells and in mature NeuN(+) granular neurons. Adult and middle-aged Cav1.3(-/-) mice showed severe impairments in dentate gyrus neurogenesis, with significantly smaller dentate gyrus volume, reduced survival of newly generated cells, and reduced neuronal differentiation. Further, Cav1.3(-/-) mice showed impairment in the hippocampus dependent object location memory test, implicating Cav1.3 as an essential element for hippocampus-associated cognitive functions. Thus, modulation of LTCC activities may have a crucial impact on neurogenic responses and cognition, which should be considered for future therapeutic administration of LTCCs modulators.

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“…Although these are likely mediated by Cav channel dysfunction in neurons, astrocytes may also play a role in disease processes. Cav1.3 (L-type) and Cav2.1 (P-type) channel expression is induced in hippocampal reactive astrocytes following pilocarpine-induced status epilepticus [104]. In APP transgenic mice, Cav1.2 channels are induced in reactive astrocytes surrounding amyloid plaques, and their expression increases with the age of mice and the number of plaques [105].…”

Section: Astrocyte Channel Proteinsmentioning

confidence: 99%

Regulation of neurovascular coupling in autoimmunity to water and ion channels

Jukkola¹,

Gu²

2015

Autoimmunity Reviews

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Much progress has been made in understanding autoimmune channelopathies, but the underlying pathogenic mechanisms are not always clear due to broad expression of some channel proteins. Recent studies show that autoimmune conditions that interfere with neurovascular coupling in the central nervous system (CNS) can lead to neurodegeneration. Cerebral blood flow that meets neuronal activity and metabolic demand is tightly regulated by local neural activity. This process of reciprocal regulation involves coordinated actions of a number of cell types, including neurons, glia, and vascular cells. In particular, astrocytic endfeet cover more than 90% of brain capillaries to assist blood-brain barrier (BBB) function, and wrap around synapses and nodes of Ranvier to communicate with neuronal activity. In this review, we highlight four types of channel proteins that are expressed in astrocytes, regarding their structures, biophysical properties, expression and distribution patterns, and related diseases including autoimmune disorders. Water channel aquaporin 4 (AQP4) and inwardly-rectifying potassium (Kir4.1) channels are concentrated in astrocytic endfeet, whereas some voltage-gated Ca2+ and two-pore-domain K+ channels are expressed throughout the cell body of reactive astrocytes. More channel proteins are found in astrocytes under normal and abnormal conditions. This research field will contribute to a better understanding of pathogenic mechanisms underlying autoimmune disorders.

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Ca_v1.2, Ca_v1.3, and Ca_v2.1 in the mouse hippocampus during and after pilocarpine‐induced status epilepticus

Cited by 46 publications

References 31 publications

PKCε upregulates voltage‐dependent calcium channels in cultured astrocytes

PKCε upregulates voltage‐dependent calcium channels in cultured astrocytes

The L-type calcium channel Cav1.3 is required for proper hippocampal neurogenesis and cognitive functions

Regulation of neurovascular coupling in autoimmunity to water and ion channels

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