Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.605022
Title: Calcium signal transduction in astrocytes
Author: James, L. R.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2011
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Abstract:
Ca2+ signals can exhibit great spatiotemporal complexity, leading to the hypothesis that the dynamics of Ca2+ signals may allow astrocytes to discriminate between stimuli. An in vitro model system of primary cerebellar and cortical astrocytes was tailored to test this hypothesis, by comparing the kinetics of the Ca2+ signal evoked by different receptor agonists. It was found that known physiological agonists triggered highly heterogeneous responses, but there were no systematic trends in the specific kinetic parameters of Ca2+ signals that depended on the agonists which triggered them. These results suggest that the encoding of information as to agonist identity in the timing of the Ca2+ signal is unlikely to be feasible. However, different agonists vary in the efficacy with which they trigger cell-wide Ca2+ signals suggesting that there is a discrete probability that cultured astrocytes will respond to a given agonist with an all-or-none Ca2+ signal. The probability of triggering a response can be enhanced by the neuromodulator nitric oxide (NO), acting through its receptor, soluble guanylyl cyclase (sGC). The mechanism of this “gain modulation” involves activation of PKG and PKC modulating an aspect of the Gq signalling pathway in a manner that increases Ca2+ excitability. Further investigations revealed complex crosstalk between the NO and Ca2+ signalling pathways at multiple levels. In summary, the kinetics of Ca2+ signalling in cultured astrocytes while heterogeneous, do not appear to vary predictably between physiological stimuli. Instead, the probability of response does vary according to receptor agonist, and can be enhanced by co-stimulation with NO. Given the close proximity between the astrocytic endfeed and CNS capillary and neuronal networks, but of which generate NO, there is potential for this crosstalk to modulate the activity of astrocytes in vivo.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.605022  DOI: Not available
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