Gap junctions equalize intracellular Na+ concentration in astrocytes

Rose, Christine R.; Ransom, Bruce R.

doi:10.1002/(sici)1098-1136(199708)20:4<299::aid-glia3>3.0.co;2-1

Cited by 126 publications

(81 citation statements)

References 36 publications

(54 reference statements)

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“…This competition for microtubule binding sites facilitated signal transduction from the TGF-␤ receptor to the nucleus and, thus, activation of target gene expression (Dai et al, 2007). Such a mechanism would be unaltered by heptanol treatment, because heptanol sterically alters the pore size of the GJ complex rather than acting on the individual connexin protein (Guan et al, 1997;Rose and Ransom, 1997;Cotrina et al, 1998). If a similar mechanism were active in the LPM, Cx43 expression in the Nodal expression domain would be involved in the activation of the Nodal target genes Nodal, Lefty, and Pitx2.…”

Section: Discussionmentioning

confidence: 99%

“…Initially, we used lindane to block GJC. Because of the toxicity of this agent, we switched to heptanol in subsequent experiments, an aliphatic alcohol known to block GJC, presumably by intercalation into the membrane and thus mechanically squeezing channels closed (Guan et al, 1997;Rose and Ransom, 1997;Cotrina et al, 1998). As heptanol proved to be an efficient agent in our experiments, other known effectors of gap junctional conductance such as octanol were not investigated (Spray et al, 1985;Harris, 2001;Rozental et al, 2001).…”

Section: Gj Are Required For Rightsided Repression and Leftsided Indumentioning

confidence: 99%

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Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Feistel

Blum

2008

Developmental Dynamics

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Section: Discussionmentioning

confidence: 99%

Section: Gj Are Required For Rightsided Repression and Leftsided Indumentioning

confidence: 99%

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Feistel

Blum

2008

Developmental Dynamics

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“…Pharmacological data indicate that the release of both ATP and glutamate are primarily responsible for the transmission mechanism as well as, to a lesser extent, gap junctions, inasmuch as Na i ϩ can equilibrate among astrocytes through gap junctions (30). The Na ϩ waves were found to coexist with Ca 2ϩ waves.…”

Section: Discussionmentioning

confidence: 99%

“…In parallel, the released glutamate is taken up by Na ϩ ͞glutamate cotransporters, resulting in Na i ϩ increases. Na ϩ has also the ability to diffuse through gap junctions (30) and participate in the Na ϩ wave extension. In essence, it appears that glutamate release͞reuptake sustains the regenerative propagation mechanism of the Na ϩ signal, whereas gap junctions mediate the passive spreading of the Na ϩ signal.…”

Section: Discussionmentioning

confidence: 99%

Astrocytes generate Na ⁺ -mediated metabolic waves

Bernardinelli

Magistretti²,

Chatton³

2004

Proc. Natl. Acad. Sci. U.S.A.

169

145

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Glutamate-evoked Na ؉ increase in astrocytes has been identified as a signal coupling synaptic activity to glucose consumption. Astrocytes participate in multicellular signaling by transmitting intercellular Ca 2؉ waves. Here we show that intercellular Na ؉ waves are also evoked by activation of single cultured cortical mouse astrocytes in parallel with Ca 2؉ waves; however, there are spatial and temporal differences. Indeed, maneuvers that inhibit Ca 2؉ waves also inhibit Na ؉ waves; however, inhibition of the Na ؉ ͞glutamate cotransporters or enzymatic degradation of extracellular glutamate selectively inhibit the Na ؉ wave. Thus, glutamate released by a Ca 2؉ wave-dependent mechanism is taken up by the Na ؉ ͞glutamate cotransporters, resulting in a regenerative propagation of cytosolic Na ؉ increases. The Na ؉ wave gives rise to a spatially correlated increase in glucose uptake, which is prevented by glutamate transporter inhibition. Therefore, astrocytes appear to function as a network for concerted neurometabolic coupling through the generation of intercellular Na ؉ and metabolic waves.

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“…However, in other CNS areas, extensive linkage of astrocytes via gap junctions has been assumed to be essential for spatial buffering (Orkand et al, 1966). In addition, gap junctions might also benefit extracellular K ϩ homeostasis attributable to net K ϩ uptake by stabilizing intracellular ion concentrations (Rose and Ransom, 1997). Direct examination of these concepts has been difficult, primarily because selective inhibition of gap junctions is currently not possible (Rozental et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus

Wallraff¹,

Köhling²,

Heinemann³

et al. 2006

J. Neurosci.

519

570

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Astrocytic gap junctions have been suggested to contribute to spatial buffering of potassium in the brain. Direct evidence has been difficult to gather because of the lack of astrocyte-specific gap junction blockers. We obtained mice with coupling-deficient astrocytes by crossing conditional connexin43-deficient mice with connexin30 Ϫ/Ϫ mice. Similar to wild-type astrocytes, genetically uncoupled hippocampal astrocytes displayed negative resting membrane potentials, time-and voltage-independent whole-cell currents, and typical astrocyte morphologies. Astrocyte densities were also unchanged. Using potassium-selective microelectrodes, we assessed changes in potassium buffering in hippocampal slices of mice with coupling-deficient astrocytes. We demonstrate that astrocytic gap junctions accelerate potassium clearance, limit potassium accumulation during synchronized neuronal firing, and aid in radial potassium relocation in the stratum lacunosum moleculare. Furthermore, slices of mice with coupling-deficient astrocytes displayed a reduced threshold for the generation of epileptiform events. However, it was evident that radial relocation of potassium in the stratum radiatum was not dependent on gap junctional coupling. We suggest that the perpendicular array of individual astrocytes in the stratum radiatum makes these cells ideally suited for spatial buffering of potassium released by pyramidal cells, independent of gap junctions. In general, a surprisingly large capacity for K ϩ clearance was conserved in mice with coupling-deficient astrocytes, indicating that gap junctiondependent processes only partially account for K ϩ buffering in the hippocampus.

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Gap junctions equalize intracellular Na+ concentration in astrocytes

Cited by 126 publications

References 36 publications

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Astrocytes generate Na ⁺ -mediated metabolic waves

The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus

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Gap junctions equalize intracellular Na+ concentration in astrocytes

Cited by 126 publications

References 36 publications

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Gap junctions relay FGF8‐mediated right‐sided repression of Nodal in rabbit

Astrocytes generate Na + -mediated metabolic waves

The Impact of Astrocytic Gap Junctional Coupling on Potassium Buffering in the Hippocampus

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Product

Resources

About

Astrocytes generate Na ⁺ -mediated metabolic waves