A5067150916- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- Receptor Mechanisms and Signaling
- Neuroscience and Neural Engineering
- Neuroscience and Neuropharmacology Research
- Sphingolipid Metabolism and Signaling
- Lipid Membrane Structure and Behavior
- Viral Infections and Immunology Research
- Cardiomyopathy and Myosin Studies
- Cellular transport and secretion
- Nitric Oxide and Endothelin Effects
- Adenosine and Purinergic Signaling
- Cardiac Ischemia and Reperfusion
- Protein Kinase Regulation and GTPase Signaling
- Cardiovascular Effects of Exercise
- Cardiac Arrhythmias and Treatments
- Photoreceptor and optogenetics research
- Atrial Fibrillation Management and Outcomes
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Cholinesterase and Neurodegenerative Diseases
- Nicotinic Acetylcholine Receptors Study
- Virus-based gene therapy research
- Erythrocyte Function and Pathophysiology
- Calcium signaling and nucleotide metabolism
Ruhr University Bochum
2008-2019
University Hospitals of the Ruhr-University of Bochum
2008
St. Josef-Hospital
2007
Novartis (Switzerland)
2004
Howard Hughes Medical Institute
2004
University of California, San Francisco
2004
Medizinische Hochschule Hannover
2003
Science Oxford
1997
La Jolla Alcohol Research
1997
Harlow College
1997
Sphingosine-1-phosphate (SPP) has attracted much attention as a possible second messenger controlling cell proliferation and motility an intracellular Ca(2+)-releasing agent. Here, we present evidence that SPP activates G protein-coupled receptor in the plasma membrane of various cells, leading to increase cytoplasmic Ca2+ concentration ([Ca2+]i), inhibition adenylyl cyclase, opening protein-regulated potassium channels. In human enbryonic kidney (HEK) potently (EC50, 2 nM) rapidly increased...
Blood plasma and serum contain factors that activate inwardly rectifying GIRK1/GIRK4 K+ channels in atrial myocytes via one or more non-atropine-sensitive receptors coupled to pertussis-toxin-sensitive G-proteins. This channel is also the target of muscarinic M2 activated by physiological release acetylcholine from parasympathetic nerve endings. By using a combination HPLC TLC techniques with matrix-assisted laser desorption ionization–time-of-flight MS, we purified identified sphingosine...
1. Activation of muscarinic K+ current (IK(ACh)) by sphingosine‐1‐phosphate (Sph‐1‐P) was studied in isolated cultured guinea‐pig atrial myocytes using whole‐cell voltage clamp. 2. Sph‐1‐P caused activation IK(ACh) with an EC50 1.2 nM. The maximal that could be activated amounted to about 90% the a saturating concentration acetylcholine (ACh, 10 microM). Sphingosine (1 microM), which can mimic signalling effects other cells, failed cause measurable IK(ACh). 3. completely suppressed cells...
Blood plasma and serum contain factors that activate inwardly rectifying GIRK1/GIRK4 K+ channels in atrial myocytes via one or more non-atropine-sensitive receptors coupled to pertussis-toxin-sensitive G-proteins. This channel is also the target of muscarinic M2 activated by physiological release acetylcholine from parasympathetic nerve endings. By using a combination HPLC TLC techniques with matrix-assisted laser desorption ionization–time-of-flight MS, we purified identified sphingosine...
1. Enzymatically isolated, cultured myocytes from hearts of adult guinea‐pigs were voltage clamped with a whole‐cell patch‐clamp technique. The pipette‐filling solution for internal dialysis contained 65 mM‐citrate and 50 microM‐EGTA as Ca2+‐chelating agents 20 mM‐Na+. Potassium channel currents blocked by replacing this ion on both sides the membrane Cs+. 2. In above conditions develop spontaneous transient inward (Iti) at constant negative holding potentials. At given potential Iti can be...
1. In quiescent preparations of guinea-pig right atria the action ACh applied in superfusion medium or released from parasympathetic nerve fibres was investigated by membrane potential measurements. 2. ACh-containing solutions induced hyperpolarizations which did not show desensitization. 3. The relationship between hyperpolarization amplitude (corrected for non-linear summation) and concentration could formally be described simple saturation kinetics with an apparent dissociation constant...
A large conductance (∼300 picosiemens) channel (LCC) of unknown molecular identity, activated by Ca(2+) release from the sarcoplasmic reticulum, particularly when augmented caffeine, has been described previously in isolated cardiac myocytes. potential candidate for this is pannexin 1 (Panx1), which shown to form ion channels expressed Xenopus oocytes and mammalian cells. Panx1 function implicated ATP-mediated auto-/paracrine signaling, a crucial role several cell death pathways suggested....
AimsApoptosis of cardiomyocytes significantly contributes to the development post-ischaemic cardiomyopathy. Although mitochondria have been suggested play a crucial role in this process, precise mechanisms controlling mitochondria-dependent apoptosis under ischaemia/reperfusion are still poorly understood. Here we aimed analyse soluble adenylyl cyclase (sAC).
Background: Inherited forms of sinus node dysfunction (SND) clinically include bradycardia, arrest, and chronotropic incompetence may serve as disease models to understand physiology impulse generation. Recently, a gain-of-function mutation in the G-protein gene GNB2 led enhanced activation GIRK (G-protein activated inwardly rectifying K + channel). Thus, human cardiac channels are important for heart rate regulation subsequently, genes encoding their subunits Kir3.1 Kir3.4 ( KCNJ3 KCNJ5 )...
1. Ratiometric confocal microscopy and the whole‐cell patch clamp technique were used to simultaneously record intracellular Ca2+ transients membrane currents from guinea‐pig ventricular myocytes. Intracellular dialysis with low‐affinity buffer citrate enabled us analyse caused by influx alone additional release sarcoplasmic reticulum (SR) in same cell. 2. In freshly isolated adult myocytes (used within 1‐4 h of isolation) both types (‘Ca2+ entry’ ‘Ca2+ release’ transients) spatially uniform...
G protein-gated inwardly rectifier K+ current in atrial myocytes (I(K(ACh))) upon stimulation with acetylcholine (ACh) shows a fast desensitizing component (t(1/2) approximately 5 s). After washout of ACh, I(K(ACh)) recovers from desensitization within < 30 s. A recent hypothesis suggests that is caused by depletion phosphatidylinositol 4,5-bisphosphate (PtIns(4,5)P(2)), resulting costimulation phospholipase C (PLC)-coupled M3 receptors (M3AChR). The effects stimulating two established...
Shortened action-potential duration (APD) and blunted APD rate adaptation are hallmarks of chronic atrial fibrillation (cAF). Basal muscarinic (M)-receptor-activated inward-rectifier K(+) currents (IK1 IK,ACh, respectively) contribute to regulation human subject cAF-dependent remodeling. Intracellular Na(+) ([Na(+)]i) enhances IK,ACh in experimental models but the effect [Na(+)]i-dependent on myocytes is currently unknown. Here, we report a inhibition outward IK1 from sinus rhythm (SR) or...
Simultaneous measurements of intracellular Ca2(+)-concentration ([Ca2+]i) using Indo-1 and the current generated by electrogenic Na+/Ca2(+)-exchange (INaCa) have been performed on atrial myocytes from hearts adult guinea-pigs. Whereas fluorescence-measurements provide information global [Ca2+]i, InaCa which is a linear function Ca2(+)-concentration, indicates subsarcolemmal [Ca2+]. Under conditions in Ca2(+)-transients due to Ca2(+)-release sarcoplasmic reticulum (SR) artificially slowed,...
Odorant receptors of zebrafish and C elegans were functionally expressed in vertebrate kidney cells (HEK293) using the eucaryotic expression vector pSMyc. Receptor-encoding cDNA cloned into this was as a fusion protein with N-terminal membrane import sequence guinea-pig serotonin receptor followed by myc tag. Immunocytochemical evidence indicates that strategy directs predicted immunoreactivity approximate molecular weight to plasma membrane. Fish food extract (TetraMin) evoked transient...
1. Spontaneous transient inward currents (Iti) caused by cyclic release of Ca2+ ions from the sarcoplasmic reticulum were studied in cultured atrial myocytes hearts adult guinea-pigs. K+ channel blocked replacing on both sides membrane Cs+; L-type current was inhibited D600. 2. The voltage dependence peak Iti and background displayed distinct outward-going rectification. I-V curves for approach each other at strongly positive potentials but do not intersect. 3. 3'-4'Dichlorobenzamil (DCB)...
Phosphoinositides constitute a critical family of lipids that regulate numerous cellular processes. Phosphatidylinositol 4,5-bisphosphate (PIP2) is arguably the most important plasma membrane phosphoinositide and involved in regulating diverse It also precursor phosphatidylinositol 3,4,5-trisphosphate (PIP3), which for growth factor signaling, as well polarization dynamics. Studying these remains challenging, because their compartmentalized activities location-dependent signaling profiles....
K<sup>+</sup> channels composed of G-protein-coupled inwardly rectifying channel (GIRK) (Kir3.0) subunits are expressed in cardiac, neuronal, and various endocrine tissues. They involved inhibiting excitability contribute to regulating important physiological functions such as cardiac frequency secretion hormones. The functional (K<sub>(ACh)</sub>) activated by G<sub>i</sub>/G<sub>o</sub>-coupled receptors muscarinic M<sub>2</sub> or purinergic A<sub>1</sub> is supposed be the GIRK1 GIRK4 a...
Most small-molecule inhibitors of voltage-gated ion channels display poor subtype specificity because they bind to highly conserved residues located in the channel's central cavity. Using a combined approach scanning mutagenesis, electrophysiology, chemical ligand modification, cross-linking, MS/MS-analyses and molecular modelling, we provide evidence for binding site adamantane derivatives their putative access pathway Kv7.1/KCNE1 channels. The compounds, exemplified by JNJ303, are potent...
G protein-activated inwardly rectifying K+ (GIRK) channels, expressed in atrial myocytes, various neurons, and endocrine cells, represent the paradigmatic target of βγ subunits released from activated heterotrimeric proteins. These channels contribute to physiological slowing cardiac frequency synaptic inhibition. They are by dimers upon stimulation receptors coupled pertussis toxin-sensitive proteins (Gi/o), whereas Gs do not converge on channel subunits. This is conflict with finding that...