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Regulation of intracellular calcium in isolated vascular smooth muscle cells

Baro-Puigdemasa, Isabelle; (1993) Regulation of intracellular calcium in isolated vascular smooth muscle cells. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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Vascular smooth muscle cells require a very precise regulation of intracellular calcium concentration, since this ion is responsible for the activation of smooth muscle contractile proteins and, subsequently, for the vascular tone. Experiments have been performed to investigate this regulation. A Ca 2+-sensitive fluorescent indicator: indo 1, has been used to measure changes of intracellular Ca2+ activity ([Ca2+]i) in enzymatically isolated smooth muscle cells of mesenteric secondary arteries from rat. Caffeine has been used to induce a Ca2+ release from the sarcoplasmic reticulum (SR) and to uncouple the SR and [Ca2+]i regulation. By means of Na+-free or La3+ -containing solutions, the relatively poor role of the Na-Ca exchange in the Ca2+ extrusion during caffeine application has been shown. Furthermore, because of its slow pumping rate, the sarcolemmal Ca 2+-ATPase contributes at a minor level to the [Ca2+]i decrease during Ca2+ load. Sarcolemmal mechanisms are responsible though for resting [Ca2+]i maintenance. Excitation-contraction coupling has been investigated. Ca2+-dependence and voltage-independence of SR Ca2+ release have been demonstrated by means of caffeine and high external K+ concentrations. Pharmacomechanical coupling of the α-adrenergic stimulation has been studied. Noradrenergic stimulation induced intracellular mobilization of Ca2+ and no contribution of extracellular Ca2+ entry to the [Ca2+]i increase could be detected. The effects of noradrenaline, caffeine and thapsigargin, allowed the description of the functional heterogeneity of the SR. Various results are in favour of the physical continuity between the IP3 sensitive and insensitive Ca2+ stores with only limited intraluminal exchanges. A model describing qualitatively and quantitatively SR refilling after Ca2+ loss is also proposed. Finally, it appears that the SR has a double function: (i) it acts as an amplifier of the external stimulations and (ii) it plays a key role in Ca2+ excess buffering.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Regulation of intracellular calcium in isolated vascular smooth muscle cells
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Intracellular calcium; Smooth muscle cells
URI: https://discovery.ucl.ac.uk/id/eprint/10105885
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