Keller, Bernhard U.

[["dc.bibliographiccitation.firstpage","322"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Pflügers Archiv - European Journal of Physiology"],["dc.bibliographiccitation.lastpage","332"],["dc.bibliographiccitation.volume","440"],["dc.contributor.author","Ladewig, T."],["dc.contributor.author","Keller, B. U."],["dc.date.accessioned","2018-11-07T10:49:31Z"],["dc.date.available","2018-11-07T10:49:31Z"],["dc.date.issued","2000"],["dc.description.abstract","Intracellular calcium signals are critical for modulation of neuronal function, and also for pathophysiological states during human neurodegenerative disease, such as Morbus Alzheimer and amyotrophic lateral sclerosis (ALS). We investigated intracellular calcium signals in motoneurones of the nucleus hypoglossus from the mouse, which were maintained in a functionally intact state of rhythmic, respiratory-related activity. Simultaneous patch-clamp recordings and calcium imaging demonstrated that rhythmic inspiratory-related clusters of action potential (AP) discharges are paralleled by calcium oscillations both in somatic and dendritic compartments. Calcium oscillations resulted primarily from the AP-induced opening of voltage-dependent calcium channels in the soma and dendrites. Dendritic calcium transients differed from somatic responses in their kinetics, amplitude, voltage dependence and regulation of basal calcium levels. Based on a combination of infrared differential interference contrast optics, microfluorimetric calcium imaging and electrophysiological patch-clamp recordings, our results demonstrate that the brainstem slice preparation is an attractive model system to study the integration and superposition of calcium signals in a functionally intact neuronal net."],["dc.identifier.doi","10.1007/s004240000277"],["dc.identifier.isi","000087884600017"],["dc.identifier.pmid","10898534"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48451"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.relation.issn","0031-6768"],["dc.title","Simultaneous patch-clamp recording and calcium imaging in a rhythmically active neuronal network in the brainstem slice preparation from mouse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Brain Research"],["dc.bibliographiccitation.lastpage","12"],["dc.bibliographiccitation.volume","1001"],["dc.contributor.author","Ladewig, T."],["dc.contributor.author","Lalley, Peter M."],["dc.contributor.author","Keller, B. U."],["dc.date.accessioned","2018-11-07T10:50:16Z"],["dc.date.available","2018-11-07T10:50:16Z"],["dc.date.issued","2004"],["dc.description.abstract","(1) Serotonin (5HT)-mediated calcium signaling was investigated in hypoglossal motoneurons (HGMs) in brain stein slices of neonatal mice. Electrical activity and associated calcium signaling were Studied by simultaneous patch clamp recordings and high resolution calcium imaging. (2) Bath application of 5HT (5-50 muM) depolarized membrane potential of HGMs and generated action potential discharges that were accompanied by elevations in intracellular calcium concentrations ([Ca2+](i)) in the soma and dendrites. Current-evoked bursts of action potentials were more intense in the presence of 5HT; however, the corresponding calcium signals were reduced. (3) The 5HT(2) receptor agonist alpha-Methyl-5HT (25, 50 muM) had effects on membrane potential, discharge properties and [Ca](i) that were identical to those observed for 5HT, whereas the 5HT(3) receptor agonist 1-(m-chlorophenyl) biguanide (50 muM) had no effect on membrane properties or intracellular calcium levels. (4) 8-OHDPAT (25, 50 muM), a 5HT(1A) receptor agonist, was without effect on steady-state membrane potential or basal [Ca](i). Similar to 5HT and alpha-Methyl-5HT, 8-OHDPAT depressed stimulus-evoked calcium transients in current and voltage clamp mode. (5) Our results suggest that calcium profiles in hypoglossal motoneurons are differentially regulated by 5HT(1A) and 5HT(2) receptors. Activation of 5HT(1A) receptors primarily reduced voltage-activated Ca2+ signals without a significant impact on basal [Ca]i. In contrast, activation of 5HT(2) receptors initiated a net inward current followed by membrane depolarization, where the resulting pattern of action potential discharges represents the essential determinant of global elevations in [Ca2+](i). Taken together, our results therefore identify 5HT-dependent signal pathways as a versatile tool to modulate hypoglossal motoneuron excitability under various physiological and pathophysiological conditions. (C) 2004 Elsevier B.V. All rights reserved."],["dc.identifier.doi","10.1016/j.brainres.2003.10.033"],["dc.identifier.isi","000220812400001"],["dc.identifier.pmid","14972649"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48616"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0006-8993"],["dc.title","Serotonergic modulation of intracellular calcium dynamics in neonatal hypoglossal motoneurons from mouse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","775"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","787"],["dc.bibliographiccitation.volume","547"],["dc.contributor.author","Ladewig, T."],["dc.contributor.author","Kloppenburg, P."],["dc.contributor.author","Lalley, Peter M."],["dc.contributor.author","Zipfel, W. R."],["dc.contributor.author","Webb, W. W."],["dc.contributor.author","Keller, B. U."],["dc.date.accessioned","2018-11-07T10:40:01Z"],["dc.date.available","2018-11-07T10:40:01Z"],["dc.date.issued","2003"],["dc.description.abstract","Hypoglossal motoneurones (HMN) are selectively damaged in both human amyotrophic lateral sclerosis (ALS) and corresponding mouse models of this neurodegenerative disease, a process which has been linked to their low endogenous Ca2+ buffering capacity and an exceptional vulnerability to Ca2+-mediated excitotoxic events. In this report, we investigated local Ca2+ profiles in low buffered HMNs by utilizing multiphoton microscopy, CCD imaging and patch clamp recordings in slice preparations. Bath application of caffeine induced highly localized Ca2+ release events, which displayed an initial peak followed by a slow 'shoulder' lasting several seconds. Peak amplitudes were paralleled by Ca2+-activated, apamin-sensitive K+ currents (I-KCa), demonstrating a functional link between Ca2+ stores and HMN excitability. The potential involvement of mitochondria was investigated by bath application of CCCP, which collapses the electrochemical potential across the inner mitochondrial membrane. CCCP reduced peak amplitudes of caffeine responses and consequently I-KCa, indicating that functionally intact mitochondria were critical for store-dependent modulation of HMN excitability. Taken together, our results indicate localized Ca2+ release profiles in HMNs, where low buffering capacities enhance the role of Ca2+-regulating organelles as local determinants of [Ca2+](i). This might expose HMN to exceptional risks during pathophysiological organelle disruptions and other ALS-related, cellular disturbances."],["dc.description.sponsorship","NCRR NIH HHS [P41-RR0422]"],["dc.identifier.doi","10.1113/jphysiol.2002.033605"],["dc.identifier.isi","000183985500006"],["dc.identifier.pmid","12562905"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/46199"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cambridge Univ Press"],["dc.relation.issn","0022-3751"],["dc.title","Spatial profiles of store-dependent calcium release in motoneurones of the nucleus hypoglossus from newborn mouse"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","82"],["dc.contributor.author","Keller, B. U."],["dc.contributor.author","Ladewig, T."],["dc.contributor.author","Kloppenburg, P."],["dc.contributor.author","Webb, W. W."],["dc.contributor.author","Zipfel, W. R."],["dc.date.accessioned","2018-11-07T10:32:50Z"],["dc.date.available","2018-11-07T10:32:50Z"],["dc.date.issued","2002"],["dc.format.extent","649A"],["dc.identifier.isi","000173252703183"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44452"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biophysical Society"],["dc.publisher.place","Bethesda"],["dc.relation.issn","0006-3495"],["dc.title","Intracellular Ca release in motoneurons that are selectively vulnerable in a mouse model of human amyotrophic lateral sclerosis as revealed by multiphoton microscopy"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]