Molecular Neurochemistry
Faculty of Chemistry and Biochemistry

Research program

Regulation of ion current density in nerve and glial cells by external factors, such as hormones and growth factors

Reactions of neurons to external stimuli ultimately result in a cell-specific firing pattern, which is governed by characteristic patterns of expression of voltage-activated ion channels, leading to individual electrical characteristics of neurons. Although this cell-type specific pattern is already found with the expression of the first neuronal markers (see e.g. Gottmann et al., 1988), to some extent the ion current pattern of a cell can be modulated by external factors, such as hormones and growth factors. We have obtained evidence, that voltage-activated Na+- currents are up regulated in postnatal hippocampal neurons by thyroid hormone leaving K+-current densities unaffected (Potthoff and Dietzel, 1997).

Current and future research aims at answering the questions, whether this regulation is a direct membrane effect or occurs via nuclear receptors, to clarify, which subtypes of channels including voltage-activated Ca2+ - channels are regulated and whether the effect is limited to specific neuronal subtypes and species. Finally, it will be of interest to study the interaction of these regulatory mechanisms with the effects of other hormones on ion channel regulation.

In addition, we have obtained evidence that voltage-gated ion channels in cultured oligodendrocytes can be regulated by neurotrophins (in collaboration with H.H. Althaus and R. Heumann). The conditions leading to an up-regulation of voltage-activated ion channels in glial cells, are however, far from understood. One goal of this research is to elucidate, to which extent the function of a neuron or glial cell is flexible and still subject to modification by external factors after the developmental decision to a specific neuronal subtype has been made.

Second, several neurologic symptoms, such as dementia and slowing of mental function occurring in consequence to postnatal hypothyroidism may find their explanation in the regulation of ion channel expression and/or function, adding new aspects to the emerging field of ion channel diseases.

Development and application of scanning ion conductance microscopy (SICM) to investigate membrane dynamics of living cells with sub-light microscopic resolution

We have developed a novel type of a scanning ion conductance microscope (SICM) which allows to image the surfaces of cultured living cells with a resolution of currently 500 nm (Mann et al., 2002). This microscope can presently be used to investigate the locomotion of cell somata and quantify net volume changes as well as simultaneously observe local movements of the membrane surface (Happel, Diploma thesis, 2003). We are now able to investigate volume changes in glial cells caused by increases in extracellular K+-concentration in culture.

Although much is known about the basic mechanisms of K+-regulation by glial cells, it is still unknown, how KCl- uptake and spatial K+-buffering combine under different geometrical constellations (see e.g. Dietzel et al., 1989). Since a KCl-uptake will cause a net cell swelling, while spatial buffering will induce a cell movement towards the K+-source SICM investigations will help to quantitatively distinguish between the activation of the different mechanisms under different experimental conditions.

In addition we plan to increase the spatial and temporal resolution of the method to investigate neurite formation and combine it with ion-selective microelectrodes, patch-clamp techniques and - in collaboration with Prof. Schuhmann's laboratory - with additional biosensors.