Projects / Programmes
Merkel cells: their role and function in detection of mechanical stimulus on skin surface
| Code |
Science |
Field |
Subfield |
| 3.03.00 |
Medical sciences |
Neurobiology |
|
| Code |
Science |
Field |
| B640 |
Biomedical sciences |
Neurology, neuropsychology, neurophysiology |
| Code |
Science |
Field |
| 3.01 |
Medical and Health Sciences |
Basic medicine |
Merkel cells, mechanoreception, sensory physiology
Researchers (1)
| no. |
Code |
Name and surname |
Research area |
Role |
Period |
No. of publicationsNo. of publications |
| 1. |
23608 |
PhD Janez Prešern |
Biology |
Head |
2011 - 2013 |
213 |
Organisations (1)
Abstract
Sense of touch is vital for an individual in many contexts, ranging from detection of physical properties of environment to complex social interactions (e.g. mother – child …). Being so important, sense of touch has attracted a lot of scientific attention and there are many applications of accumulated knowledge (props for handicapped, physiotherapeutic methods, product packaging …). Somehow surprisingly, there are still some questions regarding basics of stimulus detection, which remain unanswered. In proposed project, I will focus on some of these. Answers provided by the project might improve certain aspects of application.
Merkel complex is one of the skin mechanoreceptor types which underlie the sense of touch. Compared to other types of mechanoreceptors, like Meissner corpuscles or Pacini corpuscle, its structure seem to be relatively simple: an afferent nerve ending forming a cup-like structure and Merkel cell placed above this cup-like structure with putative synapse between them. Despite this simple blueprint, roles of its components are not clear and are often disputed. While majority of investigators agree that Merkel cell is necessary for the afferent responses to tissue displacement – at least for the constant phase of displacement – the contribution of Merkel cell to the afferent response is not known.
In my project I will determine the contribution of Merkel cell to the afferent response and build a Hodgkin&Huxley model of Merkel cell, which will serve for the investigation of mechanically activated input currents. To achieve stated goals, I will combine imaging of voltage-sensitive dyes with whole-cell patch/voltage clamp on the glabrous skin slices, obtained from mice toes/fingers. To determine relationship between Merkel cell and the afferent response, I will first manipulate its membrane potential to achieve exocytosis of neurotransmitter. This relationship will be examined further using mechanical deformations of tissue slices before and after intracellular BAPTA injection into Merkel cell. BAPTA chelator will prevent exocytosis and thus effectively block the synapse. I will evaluate the changes in the afferent response.
To build a model, I will feed identified current and channel properties already available in publications into non-stationary noise analysis to determine N of channels of each type. I will use NEURON to build simple model platform and equip it with known non-mechanically gated channels. This model platform will be used to determine the properties of mechanically activated currents, which trigger the membrane potential changes, similar to those measured with imaging and electrophysiological methods. Deformations of tissue around Merkel cells will also be modeled and correlated with input currents.
Proposed project will answer a long standing question about the actual role of Merkel cell using in situ approach. Using tissue slices is one of the advantages of my project over majority of past studies. Such approach is rare in the field of mechanoreception, likely due to historical technical difficulties. With modern research equipment, techniques and experience in tissue slices, available in the host lab, suggested in situ approach is not only feasible but also necessary.
Proposed project is basic research. However, I plan to disseminate results to other (industry-related) laboratories. That way, I expect results to contribute to improvement of application. Established network will help shaping my future work.
Significance for science
Our project noticeaby contributed to both the knowledge about the physiology of Merkel cells and also to the part of sensory physiology concerning the activation of mechanically activated ion currents due to the physical force applied on the investigated cell’s membrane. With our work we have for the first time: 1) showed and described the ion currents elicited by a direct mechanical stimulation of Merkel cell’s membrane, their properties and their dependence of stimulus amplitude, 2) showed the activation of the exocytotic machinery in Merkel cells, 3) showed that Merkel cell is able to sustain exocytosis over longer time period, which is supports the idea of the static pressure coding, 4) described the mechanical behaviour of a cell in experiments from 1) by building a finite-element model of a cell in the experiments and 5) showed that acceleration of the membrane stretch possibly isn’t the physical quantity that contributes to the opening of the stretch ion channels.
Significance for the country
Project impact can be summarized into three important points. First, the project had an important role in education of human resources. Development of models was greatly assisted by a construction engineer and a mathematician, who gained their first knowledge in modeling the biological systems. Cooperation resulted in submitted paper (see above). Second, we consider this project a pioneer in bridging the gaps and thus linking the traditionaly separated scientific fields Slovenija. We consider sensory physiology as an ideal field for convergence of biomedical and engineering know-how, what we showed by collaboration with the C3M d.o.o. Over this external partner we linked-up with potential partners in industry with some of which we plan further collaboration. Last but not least: the project promoted Slovenian know-how and successfully transplanted selected methodology into our local scientific milieu. Project ideas were first presented at the University of Gothenburg (September, 2011), where we obtained knowledge about certain aspects of work with tissues containing mechanosensitive structures which we later applied in our work. Project results were also presented at the internal conference of NanoBioTouch consortium (Birmingham, November 2013).
Most important scientific results
Final report,
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Most important socioeconomically and culturally relevant results
Final report,
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