Shen Chen

2016 AFPGR Participant

 

The Kir6.1 potassium channel: a new target to protect the heart from damage during a heart attack?
About Shen

Shen is currently a PhD student  in the Department of Cardiovascular Sciences, studying cardiac ion channel physiology. After 4 years of study in clinical science and a 1-year internship in RuiKang hospital in China, Shen graduated as a doctor, but was still interested in research. Shen continues to study, having attained an MSc from the University of Leicester and now studying for a PhD.

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About My Research

During a heart attack (myocardial infarction) a coronary artery, that is the source of the heart muscles oxygen and energy sources, becomes blocked. This lack of blood flow is termed “ischaemia” and this ischaemia is one of the causes of muscle damage. Cardioprotection is a generic term applied to any stimuli that allows the heart to recover more readily following ischaemia. Despite over 30 years of research, a definitive mechanism for this powerful protective process has yet to be elucidated. There have been a number of competing hypotheses regarding what the effector of this protection could be; one of these is the involvement of a specialised protein that allows potassium ions to move out of heart cells, the ATP-sensitive potassium (KATP) channel. Generally, moving potassium out of muscle cells helps them to relax, so this channel helps to limit how hard the heart works to spare energy.

The KATP channels in the heart have been believed to me made of two proteins Kir6.2 and SUR2A. Recently, our lab published a paper showing that this channel was not a key effector of cardioprotection, rather this channel complex simply opened in response to ATP depletion which could not cause protection (Brennan et al, 2015). My research has identified for the first time a different isoform of the KATP family that is expressed in cardiac ventricular myocytes. We believe that this novel channel may be the KATP channel that plays an important role in cardioprotection

Research Findings

In 2014 there were around 81,000 deaths in the UK caused by ischaemic heart disease each year (BHF). There are currently no pharmacological treatments that can help to reduce the injury to the cells suffered during a heart attack. This is because we do not completely understand the mechanisms of cardioprotection and so it is not clear what drugs should target!

My research has identified a new ion channel, the activity of which is massively increased in cells where cardioprotection has activated. We hypothesise that this opening causes a shortening of the cardiac action potential and hyperpolarisation of the resting membrane potential to make the cell less ‘excitable’. This helps to preserve cardiomyocyte function and energy during ischaemia so imparting cardioprotection.

In my PhD to date I have identified the subunits that make up this channel, and I have demonstrated the functional role for this channel in cardioprotection. We believe that the investigation of this new ion channel may improve our understanding of the mechanisms of cardioprotection and also provide a new target that could be used to pharmacologically protect the heart from ischaemia.

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