Beat-to-beat modulation of Calcium-induced Calcium release in cardiac muscle

Contraction in the heart is well known to be dependent on a transient rise in intracellular calcium concentration. This increase in intracellular calcium is due to calcium released from the sarcoplasmic reticulum, which is triggered by Calcium entry through L-type Calcium channels on the sarcolemmal membrane (Fabiato , 1985). The strongest evidence for calcium-induced calcium release is the voltage-dependence of the L-type calcium current and calcium release from the sarcoplasmic reticulum, both of which exhibit a bell-shaped curve (Hussain & Orchard, 1997). However, a more detailed examination of the relationship between the calcium entry through L-type calcium channels and calcium released from the sarcolplasmic reticulum shows that this relationship is not always linear i.e. changes in the amplitude of the calcium current do not always correlate with proportional changes in calcium release from the sarcolplasmic reticulum.

The primary aim of this project is to investigate the quantitative relationship between the L-type calcium current and calcium released from the sarcoplasmic reticulum on a beat-to-beat basis. These experiments will also investigate the mechanisms of calcium release in myocytes that have been modified by removal of their t-tubules (Kawai et al, 1997) and those that have been stimulated by catecholamines. Further experiments will examine whether abnormalities in calcium regulation can lead to arrhythmias (Wilson et al, 2023). The methodology to be used in this project is in demand in industry and in academia and will therefore provide useful training that will help the PhD student to develop a successful career in experimental research in the future.

How to apply

Formal applications can be submitted via the University of Bradford web site; applicants will need to register an account and select 'Full-time PhD in Biomedical Science' as the course, and then specify the project title in the 'Research Proposal' section.

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Bradford is a research-active University supporting the highest-quality research. We excel in applying our research to benefit our stakeholders by working with employers and organisations world-wide across the private, public, voluntary and community sectors and actively encourage and support our postgraduate researchers to engage in research and business development activities.

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Under sections 158-159 of the Equality Act 2010, positive action can be taken where protected group members are under-represented. At Bradford, our data show that people from Black, Asian, and Minority Ethnic groups who are UK nationals are significantly under-represented at the postgraduate researcher level. 

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