Expression of voltage-gated calcium channels in astrocytes
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AbstractIn astrocytes, calcium signaling represents a central mechanism for the integration of cellular activity, as it constitutes their principal way of intercellular communication and it mediates neurotransmitter release that will in turn modulate synaptic activity. Calcium homeostasis is therefore of fundamental importance, and the identification of the different pathways mediating calcium influx in astrocytes should constitute a focal area of investigation. While some components mediating calcium influx in astrocytes have already been thoroughly described, evidence regarding the expression of voltage-gated calcium channels in astrocytes is still limited and controversial. Since these channels are involved in many critical functions like exocytosis and the activation of multiple intracellular cascades, their investigation will bring essential insight to the physiology of astrocytes. The objective of this work was then to characterize voltage-gated calcium channel expression in astrocytes and to evaluate their regulation in malignant astrocytes. I described, using primarily molecular and biochemical techniques, voltage-gated calcium channels in astrocytes and T-type channels in glioma and characterized, with an expression system, the functional properties of two calcium channel splice variants that I have identified in these cells. I demonstrated that astrocytes express both high and low voltage-activated calcium channels and that the expression of T-type channels is regulated in glioma. I discovered that astrocytes express an R-type splice variant, previously identified in endocrine cells, and that human glioma express a novel T-type channel isoform that had not yet been observed in humans. I also discovered that annexin III associates specifically with the III-IV linker of this novel T-type isoform. Overall, these results show that astrocytes express different types of calcium channels and that T- type channels are differentially regulated in malignant astrocytes, suggesting the possibility that calcium channels significantly contribute to calcium signaling in astrocytes and that they are involved in the transformation of astrocytes into a malignant phenotype.
Bibliography: p. 158-182
CitationLatour, I. (2004). Expression of voltage-gated calcium channels in astrocytes (Unpublished doctoral thesis). University of Calgary, Calgary, AB. doi:10.11575/PRISM/17640
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