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

By A. Wallraff, R. Köhling, U. Heinemann, M. Theis, K. Willecke, C. Steinhäuser. Journal of Neuroscience, 2006

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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−/− 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+ clearance was conserved in mice with coupling-deficient astrocytes, indicating that gap junction-dependent processes only partially account for K+ buffering in the hippocampus.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/56d8f850f3b6b1b4990be656763abda5f016e3a2

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Citations in the corpus

Astrocytes: a central element in neurological diseases (2016, background): “with coupling-deficient astrocytes, due to genetic deletion of Cx30 and Cx43, display impaired clearance of K+ and glutamate as well as epileptiform activity [166, 244].”
Astroglial networks: a step further in neuroglial and gliovascular interactions (2010, methodology): “, no intercellular communication — as assessed by dye coupling experiments — was observed between astrocytes of Cx43;Cx30 double-knockout mic”
Physiology of Astroglia. (2018, unknown): “Passive membrane conductance of astrocytes is not associated with gap junctional coupling: neither pharmacological inhibition nor genetic deletion of connexins affect I–V linearity (455, 935, 1573, 1838), with the exception of the olfactory bulb (1453).”
Physiological roles of aquaporin-4 in brain. (2013, background): “Several reports indicate that the rate of K clearance is positively correlated to the peak concentration of K (195).”
Heterogeneity of Astrocytic Form and Function (2012, unknown): “Surprisingly, other than some changes in potassium homeostasis, there is little phenotype in both of these knockout mice, suggesting that either there is compensatory upregulation of other connexins or pannexin molecules in these animals, or perhaps coupling may not be as integral as once thought to”