Cellular Neurophysiology (Dr. Raul E. Guzman)


The “Cellular Neurophysiology” research group investigates the physiological and pathophysiological mechanisms of ClC-3 and ClC-4 and the CLCN3/4-associated neuropathologies caused by their mutant variants. The ultimate goal is to develop novel therapeutics strategies for patients with this rare disease

Research Topics

We aim to understand the role of endosomal ion transport for neuronal function, with focus on two endo-lysosomal transporters, ClC-3 and ClC-4, that regulate the pH and [Cl-] in multiple endosomal compartments. A group of neurodevelopmental disorders, in which slight changes in ClC-3 or ClC-4 transport functions cause epilepsy and intellectual disability as well as anxiety, depression, hyperactivity, and bipolar disorders, illustrate the importance of these transporters for higher brain functions. We use transgene technology (genetically modified mouse models and shRNA lentiviral transduction), patch-clamp electrophysiology, membrane cell capacitance measurements, carbon fiber amperometry, photolytic uncaging of intracellular calcium, molecular biology, and confocal microscopy to understand the cellular and molecular function of ClC-3 and ClC-4 in neuronal health and disease and to identify potential strategies for the treatment of CLCN3- and CLCN4-related disorders. Recently, our group efforts clarified the roles of such transporters for the vesicular mono-amine accumulation process and exocytosis and how Cl-/H+ exchangers regulate the electrical and excitability properties of neurons.


Dr. Raul Guzman


Building 15.1 / Room 154

+49 2461/61-4035

Whole-cell patch-clamp analysis of WT and mutant ClC-4 currents, using transiently transfected HEK293T mammalian cells. (Modified from Front. Mol. Neurosci. https://doi.org/10.3389/fnmol.2022.872407)
A) Excitability properties recorded from wild-type neurons at the CA2 hippocampal region using acute hippocampal slice preparation. B) Richarson staining of the hippocampal region in Wild-Type, Clcn3-/- and Clcn4-/- mice.
Amperometric recordings from wild-type, Clcn3-/- chromaffin cells and rescue experiments using different ClC-3 splice variants from double ClC-3 and ClC-5 deficient cells. (Modified from Comini, M., et al., 2022, J. Neurosci. 42 (15) 3080-3095; DOI: https://doi.org/10.1523/JNEUROSCI.2439-21.2022



• Intracellular Cl-/H+ exchangers regulate the firing pattern of pyramidal neurons at the CA2 region of the Hippocampus.

• ClC-3-associated Cl-/H+ exchange function is required for neurotransmitter accumulation in adrenal chro-maffin granules

• Phenotypic characterization of ClC-4 p.V523M knock-in mouse model.

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Last Modified: 06.10.2023