Abstract
Astrocytic endfeet are specialized cell compartments whose important homeostatic roles depend on their enrichment of water and ion channels anchored by the dystrophin associated protein complex (DAPC). This protein complex is known to disassemble in patients with mesial temporal lobe epilepsy and in the latent phase of experimental epilepsies. The mechanistic underpinning of this disassembly is an obvious target of future therapies, but remains unresolved. Here we show in a kainate model of temporal lobe epilepsy that astrocytic endfeet display an enhanced stimulation-evoked Ca2+ signal that outlast the Ca2+ signal in the cell bodies. While the amplitude of this Ca2+ signal is reduced following group I/II metabotropic receptor (mGluR) blockade, the duration is sustained. Based on previous studies it has been hypothesized that the molecular disassembly in astrocytic endfeet is caused by dystrophin cleavage mediated by Ca2+ dependent proteases. Using a newly developed genetically encoded Ca2+ sensor, the present study bolsters this hypothesis by demonstrating long-lasting, enhanced stimulation-evoked Ca2+ signals in astrocytic endfeet.
Highlights
Evidence is accruing that perivascular astrocytic endfeet are highly specialized cell compartments in terms of molecular organization and functional roles (Nagelhus and Ottersen, 2013)
GCaMP5E was expressed within all astrocytic compartments, including the fine astrocytic processes and endfeet adjacent to CD31-immunopositive blood vessels (Figure 1B)
Astrocytes are highly polarized cells, structurally as well as functionally, opening for the possibility of a compartmentation of Ca2+ signaling analogous to that found in neurons
Summary
Evidence is accruing that perivascular astrocytic endfeet are highly specialized cell compartments in terms of molecular organization and functional roles (Nagelhus and Ottersen, 2013). The endfeet are enriched in the inwardly rectifying K+ channel Kir4.1 (Nagelhus et al, 1999; Higashi et al, 2001). This channel is thought to mediate K+ siphoning in the retina (Kofuji et al, 2000) and contributes to K+ spatial buffering in the CNS at large (Chever et al, 2010; Haj-Yasein et al, 2011a). The unique features of the astrocytic endfeet imply that astrocytes are highly polarized cells, biochemically as well as functionally
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