Mironov, Sergej L.

[["dc.bibliographiccitation.firstpage","60"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Brain Research"],["dc.bibliographiccitation.lastpage","67"],["dc.bibliographiccitation.volume","853"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T10:57:54Z"],["dc.date.available","2018-11-07T10:57:54Z"],["dc.date.issued","2000"],["dc.description.abstract","K-ATP channels regulate the neuronal excitability and their activation during hypoxia/ischemia protect neurons. The activation of K-ATP channels during hypoxia is assumed to occur mainly due to the fall in intracellular ATP levels, but other intracellular signalling pathways can be also involved. We measured single K-ATP channel currents in inspiratory brainstem neurones of neonatal mice. The activity of K-ATP channels was enhanced in hypoosmotic bath solutions, or after applying negative pressure to the recording pipette. Cytochalasin B activated K-ATP, channels and prevented the effects of osmo-mechanical stress, indicating that cytoskeleton rearrangements, which occur during hypoxia, contribute to the activation of K-ATP channels. During hypoxia, extracellular levels of many neurotransmitters increase, leading to activation of corresponding metabotropic receptors that can modulate KA-rp channels. K-ATP channels were activated by GABA, agonist, baclofen, by mGLUR2/3 agonists and were inhibited by mCLUR1/5 agonists. K-ATP channels were activated by phorbol esters and were inhibited by staurosporine. These treatments did not occlude the modulating actions of mGLUR agonists, indicating that they are not mediated by protein kinase C. Activator of alpha-subunits of G-proteins Mas 7 increased and their inhibitor GPant-2 decreased the activity of K-ATP channels. In the presence of either agent, the modulatory actions of baclofen and mGLUR agonists were not observed. We conclude that K-ATP channels are modulated by G-proteins that are activated by metabotropic receptors for GABA and glutamate and their release during hypoxia complements activation of channels by osmo-mechanical stress and [ATP], depletion. (C) 2000 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0006-8993(99)02234-9"],["dc.identifier.isi","000084900200008"],["dc.identifier.pmid","10627308"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/50361"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0006-8993"],["dc.title","Intracellular signalling pathways modulate K-ATP channels in inspiratory brainstem neurones and their hypoxic activation: involvement of metabotropic receptors, G-proteins and cytoskeleton"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","114"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Experimental Cell Research"],["dc.bibliographiccitation.lastpage","127"],["dc.bibliographiccitation.volume","303"],["dc.contributor.author","Mueller, M."],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Ivannikov, M. V."],["dc.contributor.author","Schmidt, J."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T08:27:46Z"],["dc.date.available","2018-11-07T08:27:46Z"],["dc.date.issued","2005"],["dc.description.abstract","Two-photon microscopy of rhodamine 123-labeled mitochondria revealed that mitochondria of neurons cultured from mouse respiratory center form functionally coupled, dynamically organized aggregates such as chains and clusters, while single mitochondria were rarely seen. Mitochondrial chain structures predominate in dendrites, while irregularly shaped mitochondrial clusters are mostly found in the soma. Both types of mitochondrial structures showed chaotic Brownian motions and the mitochondrial chains also revealed well-directed movements. The latter dislocations were arrested upon mitochondrial depolarization or blockade of mitochondrial ATP synthesis. Depolymerization of microtubules by colchicine or nocodazole or inhibition of protein phosphatases by calyculin A disrupted mitochondrial chains and the mitochondria accumulated in the soma. Forskolin and IBMX reversibly blocked directed movements of mitochondria, but did not affect their overall spatial distribution. Thus, protein phosphorylation seems to control both mitochondrial transport and organization. Protein phosphorylation downstream of enhanced cytosolic CAMP levels apparently regulates the transition from motile to non-motile mitochondria, while phosphorylation resulting from inhibition of types 1 and 2A protein phosphatases massively disturbs mitochondrial organization. The complex phosphorylation processes seem to control the close interaction of mitochondria and cytoskeleton which may guarantee that mitochondria are immobilized at energetic hot spots and rearranged in response to changes in local energy demands. (C) 2004 Elsevier Inc. All rights reserved."],["dc.identifier.doi","10.1016/j.yexcr.2004.09.025"],["dc.identifier.isi","000226111600011"],["dc.identifier.pmid","15572032"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16270"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Inc"],["dc.relation.issn","0014-4827"],["dc.title","Mitochondrial organization and motility probed by two-photon microscopy in cultured mouse brainstem neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","166"],["dc.bibliographiccitation.issue","1-2"],["dc.bibliographiccitation.journal","Brain Research"],["dc.bibliographiccitation.lastpage","177"],["dc.bibliographiccitation.volume","869"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2021-06-01T10:50:03Z"],["dc.date.available","2021-06-01T10:50:03Z"],["dc.date.issued","2000"],["dc.description.abstract","Brief hypoxia (2 min) enhances the activity of L-type Ca2+ (Ca-L) channels. The effect is dye to glutamate release and concomitant stimulation of metabotropic glutamate receptors of the mGLUR1/5 type [22] [S.L. Mironov, D.W. Richter, L-type Ca2+ channels in inspiratory neurones and their modulation by hypoxia, J. Physiol. 512 (1998) 75-87.]. Besides increasing single channel activity, hypoxia induces a negative shift of the activation curve and slows down the inactivation of the Ca-L current. In the present study we investigated these effects further, aiming to reveal intracellular signalling pathways that mediate the coupling between mGLURs and Ca-L channels. Channel activity was recorded in cell-attached patches from inspiratory brainstem neurones of neonatal mice (PG-ll). Ca-L channels were inhibited by the mGluR2/3 agonists. mGluR1/5 agonists accelerated and mGluR2/3 agonists suppressed the respiratory output, and correspondingly modified the hypoxic response of the respiratory center. Ca-L channels were also modulated by protein kinase C-L but this did not prevent the hypoxic modification of channel activity. G-protein activators enhanced and G-protein inhibitors suppressed the Ca-L channel activity, and in the presence of these agents the effects of hypoxia were abolished. Ryanodine but not thapsigargin inhibited the channel activity and occluded the hypoxic potentiation. Only G-protein-specific agents and ryanodine prevented the slowing down of inactivation induced by hypoxia. Our data indicate that coupling between mGluR1/5 and Ca-L channels is mediated by pathways that utilize G-proteins and ryanodine receptors. Glutamate release and concomitant activation of Ca-L channels are responsible for accelerating of respiratory rhythm during early hypoxia. (C) 2000 Elsevier Science B.V. All rights reserved."],["dc.identifier.doi","10.1016/S0006-8993(00)02396-9"],["dc.identifier.isi","000087990300020"],["dc.identifier.pmid","10865071"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/86507"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Elsevier Science Bv"],["dc.relation.issn","0006-8993"],["dc.title","Hypoxic modulation of L-type Ca2+ channels in inspiratory brainstem neurones: Intracellular signalling pathways and metabotropic glutamate receptors"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The FASEB Journal"],["dc.bibliographiccitation.volume","16"],["dc.contributor.author","Mueller, M."],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Schmidt, J."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T10:31:06Z"],["dc.date.available","2018-11-07T10:31:06Z"],["dc.date.issued","2002"],["dc.format.extent","A464"],["dc.identifier.isi","000174533602569"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/44025"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Federation Amer Soc Exp Biol"],["dc.publisher.place","Bethesda"],["dc.relation.issn","0892-6638"],["dc.title","Mitochondrial organization and motility probed by twin-photon microscopy in cultured murine brainstem neurons."],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","69"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","81"],["dc.bibliographiccitation.volume","537"],["dc.contributor.author","Haller, M."],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Karschin, A."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T11:24:18Z"],["dc.date.available","2018-11-07T11:24:18Z"],["dc.date.issued","2001"],["dc.description.abstract","1.The respiratory centre within the brainstem is one of the most active neuronal networks that generates ongoing rhythmic activity. Stabilization of such vital activity requires efficient processes for activity-correlated adjustment of neuronal excitability. Recent, investigations have shown that a regulatory factor coupling electrical activity with cell metabolism comprises ATP-dependent K+ channels (K-ATP channels), which continuously adjust the excitability of respiratory neurons during normoxia and increasingly during hypoxia. 2. We used the single-cell antisense RNA amplification-polymerase chain reaction (PCR) technique to demonstrate that respiratory neurons co-express the sulphonylurea receptor SUR1 with the Kir6.2 potassium channel protein. 3. Single channel measurements on rhythmically active inspiratory neurons of the brainstem slice preparation of newborn mice revealed that K-ATP channels are periodically activated in synchrony with each respiratory cycle. 4. The Na+-K+-ATPase was inhibited with ouabain to demonstrate that oscillations of the channel open probability disappear, although respiratory activity persists for a longer time. Such findings indicate that K-ATP channel open probability reflects activity-dependent fluctuations in the ATP concentration within submembrane domains. 5. We also examined the effects of extracellular [K+] and hypoxia. All changes in the respiratory rhythm (i.e. changes in cycle length and burst durations) affected the periodic fluctuations of K-ATP. channel activity. 6. The data indicate that K-ATP channels continuously modulate central respiratory neurons and contribute to periodic adjustment of neuronal excitability. Such dynamic adjustment of channel activity operates over a high range of metabolic demands, starting below physiological conditions and extending into pathological situations of energy depletion."],["dc.identifier.doi","10.1111/j.1469-7793.2001.0069k.x"],["dc.identifier.isi","000172356100009"],["dc.identifier.pmid","11711562"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56373"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cambridge Univ Press"],["dc.relation.issn","0022-3751"],["dc.title","Dynamic activation of K-ATP channels in rhythmically active neurons"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","520"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","European Journal of Neuroscience"],["dc.bibliographiccitation.lastpage","526"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Langohr, K."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T10:21:08Z"],["dc.date.available","2018-11-07T10:21:08Z"],["dc.date.issued","2000"],["dc.description.abstract","A hyperpolarization-activated current, I-h, is often implied in pacemaker-like depolarizations during rhythmic oscillatory activity. We describe I-h in the isolated respiratory centre of immature mice (P6-P11). I-h was recorded in 15% (22/146) of all inspiratory neurons examined. The mean half-maximal I-h activation occurred at -78 mV and the reversal potential was -40 mV. I-h was inhibited by Cs+ (1-5 mm) and by organic blockers N-ethyl-1,6-dihydro-1,2-dimethyl-6-(methylimino)-N-phenyl-4-pyrimidinamine (ZD 7288; 0.3-3 mu m) and N,N'-bis-(3,4-dimethylphenylethyl)-N-methylamine (YS 035, 3-30 mu m), but not by Ba2+ (0.5 mm). The organic I-h blockers did not change the inspiratory bursts recorded from the XIIth nerve and synaptic drives in inspiratory neurons. Hypoxia reversibly inhibited I-h but, in the presence of organic blockers, the hypoxic reaction remained unchanged. We conclude that although I-h channels are functional in a minority of inspiratory neurons, I-h does not contribute to respiratory rhythm generation or its modulation by hypoxia."],["dc.identifier.doi","10.1046/j.1460-9568.2000.00928.x"],["dc.identifier.isi","000085927900010"],["dc.identifier.pmid","10712631"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42035"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Blackwell Science Ltd"],["dc.relation.issn","0953-816X"],["dc.title","Hyperpolarization-activated current, I-h, in inspiratory brainstem neurons and its inhibition by hypoxia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","181"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","The Neuroscientist"],["dc.bibliographiccitation.lastpage","198"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Richter, Diethelm W."],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Busselberg, D."],["dc.contributor.author","Lalley, Peter M."],["dc.contributor.author","Bischoff, A. M."],["dc.contributor.author","Wilken, Barbara"],["dc.date.accessioned","2018-11-07T10:49:20Z"],["dc.date.available","2018-11-07T10:49:20Z"],["dc.date.issued","2000"],["dc.description.abstract","The exchange of gases between the external environment and the organism is controlled by a neural network of medullary neurons that produces rhythmic activity that ultimately leads to periodic contractions of thoracic, abdominal, and diaphragm muscles. This occurs in three neural phases: inspiration, postinspiration, and expiration. The present article deals with the mechanisms underlying respiratory rhythm generation and the processes of dynamic adjustment of respiratory activity by neuromodulation as it occurs during normoxia and hypoxia. The respiratory rhythm originates from the \"pre-Botzinger complex\" which is a morphologically defined region within the lower brainstem. There is a primary oscillating network consisting of reciprocally connected early-inspiratory and postinspiratory neurons, whereas various other subgroups of respiratory neurons shape the activity pattern. Rhythm generation and pattern formation result from neuronal interactions within the network, that is, from cooperative adjustments of intrinsic membrane properties and synaptic processes in the respiratory neurons. There is evidence that in neonatal mammals, as well as under certain pathological situations in adult mammals, the respiratory rhythm derives from early-inspiratory burster neurons that drive inspiratory output neurons. The respiratory network is influenced by a variety of neuromodulators. Stimulation of appropriate receptors mostly activates signal pathways that converge on cAMP-dependent protein kinase and protein kinase C. Both pathways exert modulatory effects on voltage- and ligand-controlled ion channels. Many neuromodulators are continuously released within the respiratory region or accumulated under pathological conditions such as hypoxia. The functional significance of such ongoing neuromodulation is seen in variations of network excitability. In this review, the authors concentrate on the modulators serotonin, adenosine, and opioids."],["dc.identifier.isi","000087270800021"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/48407"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Sage Publications Inc"],["dc.relation.issn","1073-8584"],["dc.title","Respiratory rhythm generation: Plasticity of a neuronal network"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","PII S0022-3727(03)53816-5"],["dc.bibliographiccitation.firstpage","1747"],["dc.bibliographiccitation.issue","14"],["dc.bibliographiccitation.journal","Journal of Physics D Applied Physics"],["dc.bibliographiccitation.lastpage","1757"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Mueller, M."],["dc.contributor.author","Schmidt, J."],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T10:37:38Z"],["dc.date.available","2018-11-07T10:37:38Z"],["dc.date.issued","2003"],["dc.description.abstract","Two-photon microscopy, compared with conventional wide-field or laser scanning microscopy, offers several advantages which arise from the near-infrared excitation and the confinement of two-photon excitation to a tiny focal volume. Therefore, there is a considerable interest in optimizing the performance of two-photon laser scanning microscopes (TPLSMs). Despite the existence of several commercially available devices, there are many reasons to start ab initio. Accordingly, we set-up a TPLSM from single components, and in this report construction details of our custom-built system are given. The system was designed for simultaneous optical and electrophysiological recordings and the illumination path was optimized in view of power-delivery and laser pulse-broadening. For this purpose, a solid-state pumped, mode-locked Ti: sapphire laser was directly coupled into a modified upright microscope. The scan unit was built around commercial scanners and a Zeiss scan lens. Fluorescence was detected in non-descanned mode by a photomultiplier tube. Many mechanical parts and the software for system control and image acquisition were developed in our lab and can be readily modified according to special needs of experiments. All components are easily accessible and can be upgraded according to optical requirements. The performance is comparable to available commercial systems, but our TPLSM is superior in many aspects of cost, flexibility and versatility."],["dc.identifier.isi","000184894800019"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/45618"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Iop Publishing Ltd"],["dc.relation.issn","0022-3727"],["dc.title","Construction and performance of a custom-built two-photon laser scanning system"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","227"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","The Journal of Physiology"],["dc.bibliographiccitation.lastpage","236"],["dc.bibliographiccitation.volume","533"],["dc.contributor.author","Mironov, Sergej L."],["dc.contributor.author","Richter, Diethelm W."],["dc.date.accessioned","2018-11-07T09:04:03Z"],["dc.date.available","2018-11-07T09:04:03Z"],["dc.date.issued","2001"],["dc.description.abstract","1. We studied the functions of mitochondria and their hypoxic modulation in the brainstem slices of neonatal mice (postnatal day (P)G-ll). The measurements were made in the preBotzinger complex (pBC), a part of the respiratory centre, and in the hypoglossal (XII) nucleus. Using a CCD camera, changes in the redox state were assessed from cell autofluorescence produced by NADH and FAD, while alterations in mitochondrial membrane potential (Delta psi) and free Ca2+ concentration ([Ca2+](m)) were obtained from fluorescence signals after loading the cells with Rh123 and Rhod-2, respectively. 2. In the pBC, the cells were functionally identified by correlating the oscillations in [NADH), [FAD, Delta psi anti [Ca2+](m) with the respiratory motor output recorded, simultaneously from XII rootlets. In the inspiratory cells, NADH fluorescence showed a brief decrease followed by a slow and long-lasting increase during one oscillation period. The initial decrease in NADH fluorescence was accompanied by an increase in FAD fluorescence and coincided with Delta psi depolarization. The slow secondary increase in NADH fluorescence had a time course similar to that of the Rhod-8 signal, indicating the role of Ca2+ uptake by mitochondria in NAD and FADH reduction. 3. Brief (2-4 min) hypoxia reversibly abolished rhythmic changes in mitochondrial variables and brought them to new steady levels. In parallel, ATP-sensitive K+ (K-ATP) channels were activated and the respiratory output was depressed. The hypoglossal neurons showed much bigger increases in Delta psi and [NADH] during hypoxia than the pBC neurons, which may explain their extreme vulnerability to hypoxia. 4. We show here that mitochondrial function can be monitored in vitro in neurons constituting the respiratory neural network in slice preparations. Since mitochondrial variables demostrate specific, stereotypic fluctuations during a respiratory cycle, we suggest that mitochondrial function is modulated by spontaneous activity in the respiratory network. Therefore mitochondrial depolarization and Ca2+ uptake can contribute to the biphasic reaction of the respiratory network during hypoxia."],["dc.identifier.doi","10.1111/j.1469-7793.2001.0227b.x"],["dc.identifier.isi","000168756800026"],["dc.identifier.pmid","11351030"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25024"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cambridge Univ Press"],["dc.relation.issn","0022-3751"],["dc.title","Oscillations and hypoxic changes of mitochondrial variables in neurons of the brainstem respiratory centre of mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]