Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.746089
Title: The role of resting Ca2+ in astrocyte Ca2+ signalling
Author: King, C. M.
ISNI:       0000 0004 7229 8045
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2016
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Abstract:
Astrocytes form gap-junction coupled networks and their fine processes cover many synapses enabling astrocytes to powerfully modulate synapse function. Such modulation is thought to involve Ca2+ -dependent release of signalling molecules from astrocytes. However, astrocyte Ca2+ signalling and its role in synaptic physiology remains a matter of debate. An incomplete and mostly qualitative understanding of the fundamental mechanisms of intracellular Ca2+ signalling in astrocytes could be a knowledge-limiting factor. Previous studies predict that astrocyte resting [Ca2+] profoundly affects astrocyte Ca2+ signalling, especially IP3 and store-dependent Ca2+ transients. I therefore quantitatively investigated the role of resting [Ca2+] in shaping spontaneous and evoked Ca2+ transients in astrocytes. I used two-photon excitation fluorescence microscopy and whole-cell patch clamp to document Ca2+ signalling of individual passive astrocytes in the CA1 stratum radiatum of acute hippocampal slices in young adult rat. I used fluorescence lifetime imaging to obtain a quantitative readout of astrocyte [Ca2+] and reveal the relationship between resting [Ca2+] and Ca2+ transients. I combined these techniques with UV-uncaging of Ca2+ or Ca2+ buffer to manipulate the astrocyte resting [Ca2+] to further investigate its effect on Ca2+ signalling. Using these methods, we have found that low resting [Ca2+] were associated with smaller amplitudes of spontaneous Ca2+ transients. This was also true for metabotropic glutamate receptor agonist (DHPG) evoked Ca2+ transients when different cells or regions of interest of the same cell were compared. The well-established increase of most IP3 receptors’ open probability at higher cytosolic [Ca2+] could explain this observation. In contrast, changes of resting [Ca2+] within a single astrocyte region were associated with inverse changes in amplitude of evoked Ca2+ transients. The DHPG-induced equilibration of [Ca2+] across cytosol and store compartments could be a potential explanation for this effect. Thus, resting [Ca2+] could shape the amplitude of astrocyte Ca2+ transients by at least two distinct mechanisms.
Supervisor: Henneberger, C. ; Rusakov, D. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.746089  DOI: Not available
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