The functional effects of alterations in the human voltage-gated P/Q-type calcium channel. (360G-Wellcome-081593_Z_06_Z)

£111,824

Mutations in the P/Q-type voltage-gated neuronal calcium channel are responsible for a diverse range of episodic and progressive neurological disorders. In humans, three allelic disorders, namely episodic ataxia type 2, familial hemiplegic migraine and spinocerebellar ataxia type 6 (SCA 6) have been identified. However, mutations in this gene are increasingly emerging as a cause or susceptibility factor for other phenotypes including epilepsy. I propose to study the effects of mutations and s pice variants of the alpha 1A subunit of the P/Q- type calcium channel on calcium currents and channel kinetics in neurons. My goals are as follows. Firstly, I will identify and clone the dominant splice variants from the hippocampus, the cerebral cortex and the cerebellum. These areas were chosen as obvious aetiological substrates for disorders such as epilepsy, migraine and ataxia. Following this I will introduce mutations into these splice variants and study their biophysical properties. I n parallel with this I am working on constructing a viral vector for expression in neuronal cultures. I also propose to collaborate with other researchers in the group, who are developing new optical methods to relate presynaptic calcium signalling to transmitter release kinetics within individual nerve terminals.

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Grant Details

Amount Awarded 111824
Applicant Surname Rajakulendran
Approval Committee Clinical Interview Committee
Award Date 2007-03-26T00:00:00+00:00
Financial Year 2006/07
Grant Programme: Title Research Training Fellowship
Internal ID 081593/Z/06/Z
Lead Applicant Dr Sanjeev Rajakulendran
Partnership Value 111824
Planned Dates: End Date 2010-04-30T00:00:00+00:00
Planned Dates: Start Date 2007-05-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region Greater London
Sponsor(s) Prof Dimitri Kullmann