A5053885332- Cardiac electrophysiology and arrhythmias
- Ion channel regulation and function
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Heart Rate Variability and Autonomic Control
- Cardiac Arrhythmias and Treatments
- Calcium signaling and nucleotide metabolism
- CRISPR and Genetic Engineering
- Ion Channels and Receptors
- Virus-based gene therapy research
- EEG and Brain-Computer Interfaces
- bioluminescence and chemiluminescence research
- Receptor Mechanisms and Signaling
- ECG Monitoring and Analysis
- Photoreceptor and optogenetics research
- Phosphodiesterase function and regulation
- Cardiac pacing and defibrillation studies
- Retinal Development and Disorders
- RNA regulation and disease
- Nicotinic Acetylcholine Receptors Study
- Cardiac Ischemia and Reperfusion
- Cardiac Arrest and Resuscitation
- Cardiovascular Issues in Pregnancy
- MicroRNA in disease regulation
- Heart rate and cardiovascular health
Ludwig-Maximilians-Universität München
2014-2024
German Centre for Cardiovascular Research
2014-2024
LMU Klinikum
2014-2023
Center for Integrated Protein Science Munich
2011-2021
Max Planck Institute of Psychiatry
2013
University of Manchester
2013
The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links open access knowledgebase source and their ligands (www.guidetopharmacology.org), which more detailed views target ligand properties. Although constitutes over 500 pages, material presented substantially reduced compared...
The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. provides concise overviews, mostly tabular format, key properties approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There an emphasis on selective pharmacology (where available), plus links open access knowledgebase source targets their ligands (https://www.guidetopharmacology.org/), which more detailed views target ligand properties. Although constitutes almost...
Second messenger-induced Ca2+-release from intracellular stores plays a key role in multitude of physiological processes. In addition to 1,4,5-inositol trisphosphate (IP3), Ca2+, and cyclic ADP ribose (cADPR) that trigger the endoplasmatic reticulum (ER), nicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as cellular metabolite mediates lysosomal stores. While NAADP-induced found many tissues cell types, molecular identity channel(s) conferring this release remained...
Mitochondrial potassium channels have been implicated in myocardial protection mediated through pre-/postconditioning. Compounds that open the Ca2+- and voltage-activated channel of big-conductance (BK) a pre-conditioning-like effect on survival cardiomyocytes after ischemia/reperfusion injury. Recently, mitochondrial BK (mitoBKs) were as infarct-limiting factors derive directly from KCNMA1 gene encoding for canonical BKs usually present at plasma membrane cells. However, some studies...
Abstract It is highly debated how cyclic adenosine monophosphate-dependent regulation (CDR) of the major pacemaker channel HCN4 in sinoatrial node (SAN) involved heart rate by autonomic nervous system. We addressed this question using a knockin mouse line expressing monophosphate-insensitive channels. This displayed complex cardiac phenotype characterized sinus dysrhythmia, severe bradycardia, pauses and chronotropic incompetence. Furthermore, absence CDR leads to inappropriately enhanced...
Large genes including several CRISPR-Cas modules like gene activators (CRISPRa) require dual adeno-associated viral (AAV) vectors for an efficient in vivo delivery and expression. Current AAV vector approaches have important limitations, e.g., low reconstitution efficiency, production of alien proteins, or flexibility split site selection. Here, we present a technology based on via mRNA trans-splicing (REVeRT). REVeRT is flexible selection can efficiently reconstitute different numerous...
Loss or dysregulation of the normally precise control heart rate via autonomic nervous system plays a critical role during development and progression cardiovascular disease-including ischemic disease, failure, arrhythmias. While clinical significance regulating changes in rate, known as chronotropic effect, is undeniable, mechanisms controlling these remain not fully understood. Heart acceleration deceleration are mediated by increasing decreasing spontaneous firing pacemaker cells...
Background— Sinus node dysfunction (SND) is a major clinically relevant disease that associated with sudden cardiac death and requires surgical implantation of electric pacemaker devices. Frequently, SND occurs in heart failure hypertension, conditions lead to instability the heart. Although pathologies acquired have been studied extensively, little known about molecular cellular mechanisms cause congenital SND. Methods Results— Here, we show HCN1 protein highly expressed sinoatrial...
Catalytically inactive dCas9 fused to transcriptional activators (dCas9-VPR) enables activation of silent genes. Many disease genes have counterparts, which serve similar functions but are expressed in distinct cell types. One attractive option compensate for the missing function a defective gene could be transcriptionally activate its functionally equivalent counterpart via dCas9-VPR. Key challenges this approach include delivery dCas9-VPR, efficiency, long-term expression target gene, and...
The hyperpolarization-activated current I(h) that is generated by cyclic nucleotide-gated channels (HCNs) plays a key role in the control of pacemaker activity sinoatrial node cells heart. By contrast, it unclear whether also relevant for normal function cardiac ventricles.To study HCN3-mediated component ventricular function.To test hypothesis HCN3 regulates action potential waveform, we have and analyzed HCN3-deficient mouse line. At basal heart rate, mice deficient displayed profound...
Cav1.4 L-type Ca2+ channels are crucial for synaptic transmission in retinal photoreceptors and bipolar neurons. Recent studies suggest that the activity of this channel is regulated by Ca2+-binding protein 4 (CaBP4). In present study, we explored issue examining functional effects CaBP4 on heterologously expressed Cav1.4. We show dramatically increases availability. This effect crucially depends presence C-terminal ICDI (inhibitor Ca2+-dependent inactivation) domain absent a mutant lacking...
Activation of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels is facilitated in vivo by direct binding the second messenger cAMP. This process plays a fundamental role fine-tuning HCN channel activity and critical for modulation cardiac neuronal rhythmicity. Here, we identify pyrimidine nucleotide cCMP as another regulator channels. We demonstrate that shifts activation curves two members family, HCN2 HCN4, to more depolarized voltages. Moreover, speeds up slows down...
Abstract Abnormalities of ventricular action potential cause malignant cardiac arrhythmias and sudden death. Here, we aim to identify microRNAs that regulate the human ask whether their manipulation allows for therapeutic modulation abnormalities. Quantitative analysis microRNA targetomes in myocytes identifies miR-365 as a primary repolarizing ion channels. Action recordings patient-specific induced pluripotent stem cell-derived show elevation significantly prolongs duration derived from...
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dually gated that operated by voltage and neurotransmitters via the cAMP system. cAMP-dependent HCN regulation has been proposed to play a key role in regulating circuit behavior thalamus. By analyzing knockin mouse model (HCN2EA), which binding of HCN2 was abolished 2 amino acid exchanges (R591E, T592A), we found gating is essential for transition between burst tonic modes firing thalamic dorsal-lateral geniculate (dLGN)...
Hyperpolarization-activated cyclic nucleotide-gated channels (HCNs) in the nervous system are implicated a variety of neuronal functions including learning and memory, regulation vigilance states pain. Dysfunctions or genetic loss these have been shown to cause human diseases such as epilepsy, depression, schizophrenia Parkinson´s disease. The physiological HCN1 HCN2 analyzed using knockout mouse models. By contrast, there no studies for HCN3 so far. Here, we use HCN3-deficient (HCN3-/-)...
Abstract Several studies implicated cyclic adenosine monophosphate (cAMP) as an important second messenger for regulating nociceptor sensitization, but downstream targets of this signaling pathway which contribute to neuronal plasticity are not well understood. We used a Cre/loxP-based strategy disable the function either HCN2 or PKA selectively in subset peripheral nociceptive neurons and analyzed responses both transgenic lines. A near-complete lack sensitization was observed mutant...