Award details

Capacitative calcium entry mechanisms

Reference	BBS/E/B/54936739
Principal Investigator / Supervisor	Professor Sir Michael Berridge
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	61,620
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	30/06/1999
Duration	27 months

Abstract

Background: The entry of calcium into cells is mediated by a variety of channels. There is considerable information on voltage-operated channels and receptor-operated channels but much less is known about store-operated channels (SOCs) which are regulated by the state of filling of the internal stores. The unsolved problem concerning this capacitative calcium entry mechanism is how the empty stores communicate with the SOCs in the plasma membrane. This project aims to study the coupling mechanism by characterising the molecular and physiological properties of the calcium entry channels and how they are controlled. One of the priorities of the research will be to characterise the molecular diversity of the SOCs. Relevance: This work is relevant to the H&LS Foresight priority of Integrative Biology because this basic signalling mechanism is fundamental to our understanding of most cellular systems. It is particularly relevant to drug creation and delivery. Outputs: The likely benefit of this research is that it will provide basic information on the major calcium entry mechanisms of non-excitable cells. One of the functions of these SOCs is to re- charge the internal stores responsible for generating the calcium spikes and waves that drive cellular activity. This entry mechanism has been implicated in the function of osteoclasts, the regulation of adenylate cyclase, regulatory volume decrease and the control of cell proliferation. In the case of lymphocytes, certain forms of immunodeficiency result from a defect in calcium entry. It has also been implicated in hypertension where an increase in entry leads to increased contractility due to the larger stores of activator calcium. A better understanding of this key element of calcium signalling will be directly beneficial to our understanding of many diseased states. Exploitability: This research will be directly exploitable by providing new targets for the development of a new family of calcium channel blockers. Such inhibitors directed against the voltage- operated channels have been enormously important and there is every reason to suppose that the therapeutic potential of inhibitors directed against analogous channels in non- excitable cells will be equally important.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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