Regulation von Ionenkanälen und Gap Junctions während der Zellentwicklung [article]

Nadine Saskia Dilger, University, My, University, My
2020
Human neuronal cell material is highly needed for regenerative medicine as well as for physiological and pharmacological studies but has a very limited availability. Different approaches have been developed to transdifferentiate well-accessible and in vitro expandable cells into neuronal cells, thereby creating a neuronal cell model. To establish a sophisticated model it is imperative to know the evolved as well as the initial cells in detail and to be able to precisely assess the neuronal
more » ... s the neuronal developmental state after differentiation. Ion channels as well as gap junctions are essential for integration, function and development of cells in tissue, as they strongly influence the inter- and intracellular signalling. Thus, they affect cell communication and differentiation as well, also in neuronal tissue. The aim of this dissertation was to examine the regulation of ion channels and gap junctions during cell development on the in vitro model of neuronal transdifferentiated bone marrow-derived mesenchymal stem/stromal cells (MSCs). Untreated MSCs express the characteristic MSC markers CD73, CD90, CD105 and CD166 as well as the neuronal marker Tuj1. During small molecule-induced neuronal transdifferentiation the MSC markers were significantly down-regulated while Tuj1 was up-regulated. The neuronal transdifferentiated cells developed an electrical excitability and were able to evoke single action potentials. In MSCs as well as in the differentiated cells different isoforms of the gap junction-building connexins could be detected, whereby the expression pattern changed during differentiation. The strong gap junction coupling of the MSCs was nearly completely suppressed in the transdifferentiated cells whereas these cells showed an enhanced gap junction hemichannel activity. Upon extracellular stimulation with the neurotransmitter ATP the MSCs as well as the induced neuronal cells reacted by provoking intracellular Ca2+ signals. In MSCs, the response capacity was higher than in the neuronal cells and the Ca2+ signal was ma [...]
doi:10.15488/9878 fatcat:4rm2lqhtobdqxnaat6achppjc4