Modupe Ayeni

2016 AFPGR Participant

 

'Molecular Insights into Blood Pressure Regulation'
About Modupe

Modupe Ayeni completed her undergraduate degree in Physiology and Pharmacology at the University of Leicester graduating with a first class degree. She is now working towards completing her doctorate degree in the Department of Molecular and Cell Biology. She is supervised by Dr Noel Davies and Dr Nina Storey. Modupe is passionate about understanding science and enjoys making new discoveries about how the human body works. She especially enjoys relating her findings to undergraduate students, peers and members of the public. 

Profile portrait image
About My Research

Adequate blood supply is required to meet the metabolic demands of tissues. This is achieved by tight regulation of the diameter of arteries supplying those tissues. However, during certain diseases this key process can become hindered; thus exploring disease factors that contribute to such occurrence could be useful for preventing further complications.

Arteries are vessels which deliver oxygenated blood to the organs of the body. Their walls are lined with smooth muscle cells (SMCs) whose contractile state determines arterial diameter. Thus, relaxation of SMCs increases arterial diameter whilst their contraction reduces arterial diameter. SMCs have pores on their surface membrane called ion channels. These are proteins that enable the passage of ions, such as calcium (Ca2+) or potassium (K+) ions, in and out of cells which alters membrane potential. The state (contracted or relaxed) of SMCs is regulated by a balance between the opening and closure of these ion channels. In particular, the opening of K+ channels, which only allows the passage of K+ ions out of the cell, enhances the relaxation of SMCs by reducing Ca2+entry. This results in an increase in blood flow and a decrease in blood pressure.

Haem is an important molecule that is involved in a variety of biological processes mainly when bound to proteins. Unbound or “free haem” is generally very toxic to cells; it is broken down by enzymes called haem oxygenases. During certain diseases, such as haemorrhagic stroke or cerebral malaria, arteries can become contracted. This reduces blood flow which could lead to further complications such as brain injury. Bursting of red blood cells also occurs during such diseases. This results in the release of haem thereby increasing intracellular haem concentration. Unfortunately, during haemorrhagic stroke and other related diseases, cells are unable to regulate the amount of free haem efficiently due to its abnormally high concentration.

It is hypothesized that “free haem” may contribute to the contraction of arteries seen during diseases like haemorrhagic stroke. This could occur via the interaction of haem with K+ channels expressed in arterial SMCs.

The mechanism of interaction of haem with K+ channels to influence channel activity is poorly understood. There is also little knowledge about how its degradation product, carbon monoxide (CO), interacts with K+ channels. My aims are to examine the effects of haem and CO on the activity of SMC K+ channels and investigate the biological factors that influence these interactions.

Research Findings

Using mesenteric artery SMCs, I have been able to show that haem inhibits while CO enhances the activity of large-conductance Ca2+-sensitive potassium (BK) channels (one of several types of K+ channels present in SMCs). Surprisingly, haem application increased whole-cell BK currents with CO producing similar effect. Therefore, it is speculated that the effect of haem on whole-cell current could be mediated by CO generated from haem degradation within the cells.

Future investigations will include examining how CO binds to BK channels and how CO interacts with haem to counteract its inhibitory effect on the channel activity. Furthermore, the effects of haem and CO on ATP-sensitive potassium (KATP) channels, another type of K+ channel which plays a key role in the relaxation of SMCs, will be examined.

By the end of my PhD, I plan to have highlighted the role of haem in regulating these K+ channels. My experimental findings might also be useful for designing future therapeutic strategies for the treatment of diseases such as haemorrhagic stroke. This could reduce disease complications that result from the narrowing of arteries thereby ultimately save lives.

Presenter_Modupe Ayeni
Modupe with her poster at the 2016 Festival of Postgraduate Research

Share this page: