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Calcium currents in isolated human detrusor smooth muscle cells

Gallegos, C. R. R.; (1993) Calcium currents in isolated human detrusor smooth muscle cells. Masters thesis (M.S), UCL (University College London). Green open access

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Abstract

The inward calcium current plays a central role in excitation-contraction coupling in smooth muscle and changes to this current will not only alter muscle contractility but also the electrophysiological properties of the tissue. Changes to extracellular and intracellular pH have profound effects on detrusor contractility and alterations to pH may occur in vivo as a result of changes in the urinary constituents and altered blood flow during bladder distension. It was the aim of this thesis to measure the effects of pH changes on the calcium current in order to determine if this was the site of action responsible for the inotropic effects of H +. Furthermore the calcium current characteristics may also explain previous differences in the behaviour of muscle strips from patients with abnormal bladders. Experiments were performed using isolated human detrusor smooth muscle cells produced from the enzymic dissociation of biopsy samples. Intracellular pH was measured in cells loaded with the fluorochrome BCECF using epifluorescence microscopy and the inward calcium current was measured using the whole-cell patch-clamp technique with caesium chloride filled microelectrodes. It was found that changes to extracellular pH altered the calcium current in a manner consistent with the effects on contractility but the same relationship did not hold true for changes to intracellular pH. Although changes to either intracellular or extracellular pH produced significant changes to the magnitude of the calcium current no alteration to either the steady-state or time dependent kinetics was demonstrated. A group of patients was also identified with cellular hypertrophy in which the current density was significantly reduced and this was accompanied by significant differences to both the time dependent and steady-state kinetics. These findings were consistent with those reported in other hypertrophied tissues and with previous data from experiments on isolated detrusor smooth muscle strips. In a similar manner significant differences were also identified for a group of cells from patients with detrusor instability. Whilst all these experiments were performed in cells from male patients significant differences were also found in the current density of cells from female patients. Such differences in the properties of calcium channels in the human detrusor may have important therapeutic implications regarding the pharmacological treatment of abnormal contractile states.

Type: Thesis (Masters)
Qualification: M.S
Title: Calcium currents in isolated human detrusor 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; Calcium currents; Smooth muscle cell
URI: https://discovery.ucl.ac.uk/id/eprint/10105865
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