Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.596924
Title: Regulation of Ca2+ entry and Ca2+ efflux in smooth muscle cell lines
Author: Broad, L. M.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 1997
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Abstract:
In many cells, agonists that stimulate formation of inositol 1,4,5-trisphosphate (IP3) mobilise intracellular Ca2+ stores and activate several Ca2+ transport pathways in the plasma membrane. This thesis addresses the characteristics and regulation of these hormone-activated Ca2+ transport pathways in Fura 2-loaded vascular smooth muscle cell lines. The effect of cellular differentiation on the capacitative Ca2+ entry pathway in BC3Hl cells was studied using thapsigargin to empty the intracellular Ca2+ stores. Undifferentiated BC3H1 cells exhibited Ca2+ mobilisation in response to IP3 only, whereas differentiated cells responded to IP3, or to caffeine and ryanodine. Although both differentiated and undifferentiated cells expressed a capacitative Ca2+ entry pathway, the bivalent cation selectivity of the pathways differed. In undifferentiated cells, large capacitative Ca2+ entry signals were accompanied by relatively small Mn2+ and Ba2+ entry signals; the converse was true of differentiated cells. The relative increase in Mn2+ and Ba2+ permeability in differentiated cells was not a consequence of more active Ca2+ extrusion. The change in behaviour of the pathway after differentiation may result either from expression of a different capacitative pathway or from modification of the permeation properties of a single pathway. Stimulation of a7r5 cells with arginine-vasopressin (AVP) activated both a capacitative and non-capacitative Ca2+ entry pathway in the plasma membrane, only the latter was permeable to Sr2+. AVP also stimulated Ca2+ removal from the cytoplasm. The ability of other receptors that stimulate phosphoinositidase C to activate the non-capacitative pathway, its susceptibility to inhibition by a PIC inhibitor (U73122), and the similar sensitivities of Ca2+ release and Sr2+ entry to AVP suggested a close coupling between stimulation of PIC and activation of this pathway. This work has revealed that Ca2+ mobilisation, multiple capacitative and non-capacitative Ca2+ entry pathways and Ca2+ efflux all contribute to the complexity of receptor-activated Ca2+ signalling.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.596924  DOI: Not available
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