46 Dokumente gefunden

Crosstalk of KCNH1 and KCNH5 gain-of-function mutations leading to epilepsy and neurodevelopmental disorders

Voltage-gated K + (Kv) channels are tetrameric complexes of proteins encoded by KCN genes. Gain-of-function (GoF) mutations in KCNH1 (Kv10.1, hEAG1) and KCNH5 (Kv10.2, hEAG2) give rise to developmental disorders, intellectual disability, and epilepsy. Currently, clinical symptoms are not straightforwardly…
London: BioMed Central, 2026-02-08

Exceptionally selective voltage-sensor trapping of Na V 1.5 channels by Mg-protoporphyrin impairs cancer cell migration

Abstract The human voltage-gated sodium channel hNa V 1.5 is essential for cardiac excitability. Though underrecognized, Na V 1.5 is also expressed in multiple cancers, promoting cell migration and malignancy. hNa V 1.5 is a therapeutic target but limited pharmacological isoform specificity presents…
London: Macmillan Publishers Limited, part of Springer Nature, 2026-01-29

Absolute Membrane Potential Recording with ASAP-Type Genetically Encoded Voltage Indicators Using Fluorescence Lifetime Imaging

The electrical membrane voltage ( V m ) characterizes the functional state of biological cells, thus requiring precise, noninvasive V m -sensing techniques. While voltage-dependent fluorescence intensity changes from genetically encoded voltage indicators (GEVIs) indicate V m changes, variability in…
Washington, DC: American Chemical Society, 2025-11-22

Einzelmolekülfluoreszenzmessungen an nicht-aktivierten HCN2-Kanälen in natürlichen Zellmembranen

In der vorliegenden Arbeit wurde die Modulation der Bindungsaffinität an nicht-aktivierten HCN2-Kanälen untersucht. Diese nicht-selektiven Ionenkanäle werden durch Hyperpolarisation aktiviert und sorgen durch Kationeneinstrom für eine Depolarisation der Zelle. Für den nicht-aktivierten Kanal ist umstritten,…

Assoziationseigenschaften von Sphingosin-1-phosphat (S1P) und Serumalbumin (SA) in Sepsispatienten

Das Sphingosin-1-phosphat (S1P) ist ein Signalmolekül, das die Endothelbarriere stabilisiert und somit den pathophysiologischen Prozessen einer Sepsis entgegenwirkt. Es ist gebunden an Serumalbumin (SA) und High Density Lipoprotein (HDL). Bei Sepsispatienten ist die Plasmakonzentration von S1P signifikant…

Functional and structural mechanisms involved in anti-NMDAR encephalitis

Die N-Methyl-D-Aspartat-Rezeptoren (NMDARs) sind entscheidend für die synaptische Plastizität und Gedächtnisbildung. Eine Fehlregulation ihrer Funktion führt zu verschiedenen neurologischen und psychiatrischen Erkrankungen. Eine solche Erkrankung, bei der die NMDARs von Autoantikörpern (aAbs) angegriffen…

Characterization of Drosophila olfactory sensory neuron performance

Insects’ sense of smell plays a crucial role in detecting and distinguishing array of volatile chemical compounds that are present in the environment. They detect such volatile chemical compounds with great sensitivity and efficiency with the help of their olfactory sensory organs- the antenna and the…

Non-canonical sensory biology of antennal cells in insect olfaction

Insect olfaction is underpinned by antennae, organs featuring hair-like structures called sensilla. Sensilla are specialized compartments composed of a highly conserved cytological architecture, featuring an extracellular lymph and various neuronal and non-neuronal cells. Though the sensory contribution…

Peripheral temperature dysregulation associated with functionally altered Na V 1.8 channels

The voltage-gated sodium channel Na V 1.8 is prominently expressed in the soma and axons of small-caliber sensory neurons, and pathogenic variants of the corresponding gene SCN10A are associated with peripheral pain and autonomic dysfunction. While most disease-associated SCN10A variants confer gain-of-function…
Berlin Heidelberg: Springer, 2023-09-11

Intracellular hemin is a potent inhibitor of the voltage-gated potassium channel Kv10.1

Abstract Heme, an iron-protoporphyrin IX complex, is a cofactor bound to various hemoproteins and supports a broad range of functions, such as electron transfer, oxygen transport, signal transduction, and drug metabolism. In recent years, there has been a growing recognition of heme as a non-genomic…
London: Macmillan Publishers Limited, part of Springer Nature, 2022-08-27

Messung und Modulation membrannaher Prozesse in menschlichen Zellen mit optischen Methoden

Eine jede lebende Zelle hält an ihrer Plasmamembran ein elektrisches Ruhemembranpotential aufrecht, welches entscheidende Rollen u. a. bei der neuronalen Signalweiterleitung oder elektrogenen Transportprozessen einnimmt. In dieser Arbeit wurden dazu ratiometrische, genetisch codierte Spannungssensoren…

Characterization and regulation of insect odorant receptors

The olfactory world of insects is highly dynamic. Volatiles, once emitted from the source, are dispersed and diluted in the ambient air. Using a set of ∼60 odorant receptors (ORs), the fruit fly Drosophila melanogaster is able to extract valuable information from the plume in terms of odor identity and…

Monitoring of compound resting membrane potentials of cell cultures with ratiometric genetically encoded voltage indicators

Abstract The cellular resting membrane potential ( V m ) not only determines electrical responsiveness of excitable cells but also plays pivotal roles in non-excitable cells, mediating membrane transport, cell-cycle progression, and tumorigenesis. Studying these processes requires estimation of V m ,…
London: Springer Nature, 2021-10-07

Monitoring of methionine oxidation with fluorescent proteins

Methionine (Met) oxidation to methionine sulfoxide (MetO) is a post-translational protein modification that can appear unspecifically during exposure of Met to oxidants in normal growth and oxidative stress, such as occurring in aged organisms and in various degenerative diseases and pathologies. The…

Impact of intracellular hemin on N-type inactivation of voltage-gated K + channels

N-type inactivation of voltage-gated K + channels is conferred by the N-terminal “ball” domains of select pore-forming α subunits or of auxiliary β subunits, and influences electrical cellular excitability. Here, we show that hemin impairs inactivation of K + channels formed by Kv3.4 α subunits as well…
Berlin Heidelberg: Springer, 2020-05

Modulation of A-type potassium channels by stress mediators

A-type voltage-gated potassium (Kv) channels open on membrane depolarization and undergo subsequent rapid inactivation with importance in fine-tuning of cellular excitability. To serve diverse cellular needs, the inactivation is regulated by numerous mechanisms; for example, cysteine residues in the…

Structural investigations on heme-interacting proteins

Heme is a widely known cofactor molecule in many enzymes like hemoglobin, cytochromes, and myoglobins. It is attached to these proteins covalently and classifies them as hemoproteins. In the last decade, a growing number of reports on the regulatory role of heme in various molecular and cellular processes…

Contribution of somatostatin interneurons to correlated neuronal activity in the developing hippocampus

Frühe korrelierte neuronale Aktivität tritt in Form synchroner Bursts von Aktionspotentialen in großen Zellpopulationen und in allen Teilen des sich entwickelnden Gehirns auf. Eine wachsende Zahl an Studien legt nahe, dass synchrone Aktivität einen wichtigen Beitrag zur Reifung des neuronalen Netzwerks…

Detection of small biomolecules by plasmonic nanoparticles (LSPR-sensing)

Metal nanostructures with their attractive optical properties are of great interest in the field of biosensing. In this thesis, a label-free online detection of biomolecules with immobilized nanoparticles in a microfluidic chamber was realized. Two label-free sensor arrangements based on densely adsorbed…

Voltage-gated sodium channels as non-photonic sensors for membrane-delimited reactive species

Reactive species (RS) play important roles in vital physiological processes. However, excessive RS damages cells and may contribute to the onset of several diseases. Therefore, there is a clear demand for sensitive probes that precisely monitor cellular RS with a high spatio-temporal resolution to understand…