Changes in the gene and protein expression of KATP channel subunits in the hippocampus of rats subjected to picrotoxin-induced kindling

Jiang, Kewen; Shui, Quan-Xiang; Xia, Zhezhi; Yu, Zhongshen

doi:10.1016/j.molbrainres.2004.06.005

Cited by 14 publications

(10 citation statements)

References 20 publications

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“…Furthermore, we found that opening of astrocytic mitoK ATP channels alleviated neurotoxin-induced dysfunction of GJIC in cultured astrocytes and increased GJ coupling after seizure in vivo. Together, our results indicated that the anticonvulsant action of mitoK ATP channel openers [15] stemmed, probably in part, from upregulating the astrocytic GJ coupling against the seizure generation as well as adjusting the astrocytic GJ coupling against the seizure propagation, in addition to the opening neuronal K ATP channels to limit cell excitability. Our results indicate that local alterations in K ATP channel function could have variable effects on the actual level of hyperactivity in the epileptic brain.…”

Section: Astrocytic K Atp Channels and Astrocytic Gjs In Epileptogenesismentioning

confidence: 73%

“…PTX kindling was done as described [15,34] . Briefly, rats (n = 110) received a daily injection (i.p.)…”

Section: Animals and Long-term Ptx Kindling Protocolsmentioning

confidence: 99%

“…It has been reported that neuronal K ATP channels show an ability to adjust cell excitability [11][12][13] . Pharmacological and genetic studies have provided evidence to further support the roles of neuronal K ATP channels in the control of neuronal excitability and seizure propagation by depolarizing presynaptic neuron and subsequently by inhibiting the release of excitatory neurotransmitter, or by regulating GABA transporters [1,[14][15][16][17][18][19] . However, little is known about the roles of astrocytic sK ATP /mitoK ATP channels in epileptogenesis.…”

Section: Astrocytic K Atp Channels and Astrocytic Gjs In Epileptogenesismentioning

confidence: 99%

“…Manipulation of the K ATP channel status in various cellular types and at various intracellular locations has shown a variety of functional roles [3,[7][8][9][10] . It has been revealed that neuronal K ATP channels in the brain are involved in the control of neuronal excitability [11][12][13] and seizure propagation [1,[14][15][16][17][18][19] . The roles that glial K ATP channels play are receiving renewed attention due to improved understanding of the molecular events underpinning the physiological functions of glial cells.…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Gap Junctional Communication by Astrocytic Mitochondrial K<sub>ATP</sub> Channels following Neurotoxin Administration in in vitro and in vivo Models

et al. 2011

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It is known that neuronal ATP-sensitive potassium (K_ATP) channels and astrocytic gap junctions (GJs) are involved in the mechanism underlying neurodisorders. The K_ATP channels exist also in glial cells, and the objective of this study was to determine whether the astrocytic K_ATP channels exert their effect on neurotoxin-induced neurodysfunction through regulating the astrocytic GJ function. The results showed that diazoxide, a selective mitochondrial K_ATP (mitoK_ATP) channel opener, enhanced the GJ coupling, but 5-hydroxydecanoate, a selective mitoK_ATP channel blocker that significantly inhibits GJ coupling in vitro did not. Activation of astrocytic mitoK_ATP channels alleviated kainic acid-induced dysfunction of GJ intercellular communication. Finally, activation of mitoK_ATP channels improved the astrocytic GJ coupling in the hippocampus after seizures due to the colabeling of GJ subunit connexin 43 and connexin 45 with glial marker and was increased substantially by the administration of diazoxide. Western blot demonstrated that the mitoK_ATP channels regulated the expression of connexin 43 (P2; active form) and connexin 45 in the epileptic hippocampus. These findings demonstrate that activation of astrocytic mitoK_ATP channels improves the GJ function in astrocytes, indicating that the effect of the astrocytic mitoK_ATP channels on neurotoxin-induced neurodysfunction might be, in part, through the regulation of the GJ-coupled spatial buffering in the hippocampus.

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Section: Astrocytic K Atp Channels and Astrocytic Gjs In Epileptogenesismentioning

confidence: 73%

“…PTX kindling was done as described [15,34] . Briefly, rats (n = 110) received a daily injection (i.p.)…”

Section: Animals and Long-term Ptx Kindling Protocolsmentioning

confidence: 99%

Section: Astrocytic K Atp Channels and Astrocytic Gjs In Epileptogenesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Regulation of Gap Junctional Communication by Astrocytic Mitochondrial K<sub>ATP</sub> Channels following Neurotoxin Administration in in vitro and in vivo Models

et al. 2011

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“…We next sought to determine whether the reduction in barium‐sensitive, inwardly rectifying current in Tsc1 GFAP CKO astrocytes was associated with reduced expression of specific Kir‐channel proteins. Western blot analysis of extracts from astrocyte cultures was performed by using antibodies to three Kir‐channel protein subtypes present in brain astrocytes: Kir2.1, Kir4.1, and Kir6.1 (37–44). These experiments demonstrate that the reduction in barium‐sensitive current in cultured Tsc1 GFAP CKO astrocytes was associated with reduced expression of Kir‐channel proteins 2.1 and 6.1, whereas Kir4.1 expression was unaffected (Fig.…”

Section: Resultsmentioning

confidence: 99%

Epileptogenesis and Reduced Inward Rectifier Potassium Current in Tuberous Sclerosis Complex‐1–Deficient Astrocytes

et al. 2005

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Summary:Purpose: Individuals with tuberous sclerosis complex (TSC) frequently have intractable epilepsy. To gain insights into mechanisms of epileptogenesis in TSC, we previously developed a mouse model of TSC with conditional inactivation of the Tsc1 gene in glia (Tsc1 GFAP CKO mice). These mice develop progressive seizures, suggesting that glial dysfunction may be involved in epileptogenesis in TSC. Here, we investigated the hypothesis that impairment of potassium uptake through astrocyte inward rectifier potassium (Kir) channels may contribute to epileptogenesis in Tsc1 GFAP CKO mice. Methods: Kir channel function and expression were examined in cultured Tsc1-deficient astrocytes. Kir mRNA expression was analyzed in astrocytes microdissected from neocortical sections of Tsc1 GFAP CKO mice. Physiological assays of astrocyte Kir currents and susceptibility to epileptiform activity induced by increased extracellular potassium were further studied in situ in hippocampal slices.Results: Cultured Tsc1-deficient astrocytes exhibited reduced Kir currents and decreased expression of specific Kir channel protein subunits, Kir2.1 and Kir6.1. mRNA expression of the same Kir subunits also was reduced in astrocytes from neocortex of Tsc1 GFAP CKO mice. By using pharmacologic modulators of signalling pathways implicated in TSC, we showed that the impairment in Kir channel function was not affected by rapamycin inhibition of the mTOR/S6K pathway, but was reversed by decreasing CDK2 activity with roscovitine or retinoic acid. Last, hippocampal slices from Tsc1 GFAP CKO mice exhibited decreased astrocytic Kir currents, as well as increased susceptibility to potassium-induced epileptiform activity.Conclusions: Impaired extracellular potassium uptake by astrocytes through Kir channels may contribute to neuronal hyperexcitability and epileptogenesis in a mouse model of TSC.

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Glucose and hippocampal neuronal excitability: Role of ATP‐sensitive potassium channels

Huang

Cheng

et al. 2007

J of Neuroscience Research

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Hyperglycemia-related neuronal excitability and epileptic seizures are not uncommon in clinical practice. However, their underlying mechanism remains elusive. ATP-sensitive K(+) (K(ATP)) channels are found in many excitable cells, including cardiac myocytes, pancreatic beta cells, and neurons. These channels provide a link between the electrical activity of cell membranes and cellular metabolism. We investigated the effects of higher extracellular glucose on hippocampal K(ATP) channel activities and neuronal excitability. The cell-attached patch-clamp configuration on cultured hippocampal cells and a novel multielectrode recording system on hippocampal slices were employed. In addition, a simulation modeling hippocampal CA3 pyramidal neurons (Pinsky-Rinzel model) was analyzed to investigate the role of K(ATP) channels in the firing of simulated action potentials. We found that incremental extracellular glucose could attenuate the activities of hippocampal K(ATP) channels. The effect was concentration dependent and involved mainly in open probabilities, not single-channel conductance. Additionally, higher levels of extracellular glucose could enhance neuropropagation; this could be attenuated by diazoxide, a K(ATP) channel agonist. In simulations, high levels of intracellular ATP, used to mimic increased extracellular glucose or reduced conductance of K(ATP) channels, enhanced the firing of action potentials in model neurons. The stochastic increases in intracellular ATP levels also demonstrated an irregular and clustered neuronal firing pattern. This phenomenon of K(ATP) channel attenuation could be one of the underlying mechanisms of glucose-related neuronal hyperexcitability and propagation.

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Changes in the gene and protein expression of KATP channel subunits in the hippocampus of rats subjected to picrotoxin-induced kindling

Cited by 14 publications

References 20 publications

Regulation of Gap Junctional Communication by Astrocytic Mitochondrial K<sub>ATP</sub> Channels following Neurotoxin Administration in in vitro and in vivo Models

Regulation of Gap Junctional Communication by Astrocytic Mitochondrial K<sub>ATP</sub> Channels following Neurotoxin Administration in in vitro and in vivo Models

Epileptogenesis and Reduced Inward Rectifier Potassium Current in Tuberous Sclerosis Complex‐1–Deficient Astrocytes

Glucose and hippocampal neuronal excitability: Role of ATP‐sensitive potassium channels

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