Why does ageing encourage the cardiac pacemaker to fail? (360G-Wellcome-086998_Z_08_Z)
This work will take advantage of recent advances in the understanding of how the cardiac pacemaker works and preliminary data revealing why it might fail in order to gain mechanistic insight into why pacemaker dysfunction is prevalent in the elderly. Cardiac pacemaker dysfunction increases in incidence in an age-dependent manner, even with apparently healthy ageing. This necessitates treatment using artificial pacemakers to prevent the associated incidence of sudden death, exercise intolerance and atrial arrhythmias. An associated problem is an age-dependent reduction in pacemaker response to adrenergic stimulation reducing cardiac responsiveness to stress. Using a rat model of ageing changes in the expression and activity of key proteins involved in cardiac pacemaking will be mapped across the lifespan. Key aspects to be investigated are: 1) Whether processes involved in the new theory of cardiac pacemaking, regulating spontaneous releases of intracellular calcium, change with age . 2) Whether other classical moderators of pacemaker function are changing with age. 3) Whether the decline in response to adrenergic stimulation is due to changes in the phosphorylation response of specific proteins involved in the regulation of depolarisation. 4) Can changes in the activity of specific protein kinases be correlated with age-dependent changes offering routes to intervention?
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Grant Details
Amount Awarded | 74993 |
Applicant Surname | Lancaster |
Approval Committee | Physiological Sciences Funding Committee |
Award Date | 2009-02-11T00:00:00+00:00 |
Financial Year | 2008/09 |
Grant Programme: Title | Project Grant |
Internal ID | 086998/Z/08/Z |
Lead Applicant | Dr Matthew Lancaster |
Partnership Value | 74993 |
Planned Dates: End Date | 2010-10-31T00:00:00+00:00 |
Planned Dates: Start Date | 2009-11-01T00:00:00+00:00 |
Recipient Org: Country | United Kingdom |
Region | Yorkshire and the Humber |