Difference between revisions of "Team:KU Leuven/Description"

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                                 The human heart beats over a billion times during a human lifespan, while rarely skipping a beat. This fascinating organ can readily adapt its rhythm and contractility to physiological changes, e.g. a fight-or-flight reaction. Most of the changes in contractility and frequency are mediated by effectors such as epinephrine or acetylcholine.
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                                 The human heart beats over a billion times during a human lifespan, rarely skipping more than a beat. This fascinating organ can readily adapt its rhythm and contractility to physiological changes, e.g. a fight-or-flight reaction. Most of the changes in contractility and frequency are mediated by effectors such as epinephrine or acetylcholine.
 
                                 The rhythm of the human heart is usually dictated by the primary pacemaker, which consists of a group of cells termed the “pacemaker” cells, located in the in the Sinoatrial Node. The reason the primary pacemaker dictates the rhythm is mainly because it has the fastest frequency, while the backup/alternative systems such as the atrioventricular node and the Purkinje fibers operate at a slower rhythm.
 
                                 The rhythm of the human heart is usually dictated by the primary pacemaker, which consists of a group of cells termed the “pacemaker” cells, located in the in the Sinoatrial Node. The reason the primary pacemaker dictates the rhythm is mainly because it has the fastest frequency, while the backup/alternative systems such as the atrioventricular node and the Purkinje fibers operate at a slower rhythm.
 
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                                 Our team was intrigued by the way that such a tiny group of cells could have such a rapid and profound impact on the frequency of the heart. These properties inspired us to recreate a system based on the remarkable pacemaker cells.
 
                                 Our team was intrigued by the way that such a tiny group of cells could have such a rapid and profound impact on the frequency of the heart. These properties inspired us to recreate a system based on the remarkable pacemaker cells.
 
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                            <h4>The sinoatrial cell</h4>
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                                The origin of stable oscillations in sinoatrial cells is a topic that is widely debated. One hypothesis states that the internal calcium cycling is the most important factor contributing to the stable rhythm, while others suggest that the oscillating membrane potential has the biggest influence on the pacing. Experimental data as well as computational simulations support both hypotheses, depending on the experimental setup. Current understanding suggests that both systems are simultaneously responsible for maintaining a stable rhythm.
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                                The slow upstroke is mediated by both HCN and calcium channels, while the fast upstroke is mediated mostly by calcium channels. On the other hand, the repolarization is mainly mediated by potassium outflux.
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Revision as of 19:50, 28 September 2017

Project

HEKcite! Inspired by the human heart rhythm, we aim to create an electrophysiological oscillator from eukaryotic cells. Rhythmic contraction of heart cells is coordinated by a small group of cells located in the sinus node, which have an intrinsic frequency of de- and repolarization. This frequency of electrical oscillation is influenced by environmental parameters as well as certain molecular substrates. The oscillator that we aim to create consists of genetically modified excitable Human Embryonic Kidney (HEK) cells, altered to contain the intrinsic pacemaker ability found in sinus cells. As witnessed in heart cells, the rhythm would be dependent on substrate-activated ion channels in the membrane. As there is a great variety of ion channels available in nature, the oscillator could be modified to measure concentrations of many specific substrates. By integrating a certain ion channel into the oscillating system, specificity for a substrate can be chosen. Building an electrical oscillator from cells has several advantages. Intra- or extracellular changes that influence the conductance of ion channels in the membrane have an immediate impact on the frequency of oscillation. Once these cells are connected to each other (by for example gap-junctions), they generate an electrical signal that can easily be measured from a distance and non-invasively—similar to the way electrocardiography (ECG) and electroencephalography (EEG) measure electrical activity in the heart and brain. A multi-purpose sensor suitable for this system could be developed for medical and biotechnological applications. One such application is the measurement of drugs that interact with ion channels, such as antipsychotics, anti-epileptics or a certain class of immunosuppressants.


Inspired by the heart

We drew our inspiration from the versatility and robustness of the heart. It beats continuously over the years, rapidly adapting its pace when necessary.

Creation of the Rhythm

We drew our inspiration from the versatility and robustness of the heart. It beats continuously over the years, rapidly adapting its pace when necessary.

Biosensing

Finally, we aim to influence the pace by varying concentrations of biological effectors. Our main focus is establishing a new form of therapeutic drug monitoring.