Thomas Noack | University of Rostock (original) (raw)
Papers by Thomas Noack
Investigative Ophthalmology & Visual Science, 2016
Nieren- und Hochdruckkrankheiten
Cellular Physiology and Biochemistry
This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 I... more This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
Trace Elements and Electrolytes
Pflügers Archiv - European Journal of Physiology
Class-I-antiarrhythmics like ajmaline are known to alter smooth muscle function, which may cause ... more Class-I-antiarrhythmics like ajmaline are known to alter smooth muscle function, which may cause alterations in gastrointestinal motility. The effects of ajmaline on isolated gastric and portal vein smooth muscle and the underlying mechanisms are unknown. We studied the effects of ajmaline on the contractile patterns of isolated preparations of gastric antrum and portal vein from Wistar rats. The organ bath technique was used to measure spontaneous or pharmacologically induced isometric contractions. Changes in force observed after application of ajmaline or under control conditions are reported as % of the amplitude of an initial K +-induced contraction. Electric field stimulation was used to study neurogenic relaxations of gastric fundus smooth muscle. Ajmaline increased the amplitude of spontaneous contractions of muscle strips (portal vein: control 31.1 ± 15.2%, with 100 μM ajmaline 76.6 ± 32.3%, n = 9, p < 0.01; gastric antrum: control 9.5 ± 1.6%, with 100 μM ajmaline 63.9 ± 9.96%, n = 14, p < 0.01). The frequency of spontaneous activity was reduced in portal vein, but not in gastric antrum strips. The effects of ajmaline were not blocked by tetrodotoxin, L-nitroarginine methyl ester, or atropine. Ajmaline abolished coordinated neurogenic relaxations triggered by electric field stimulation and partly reversed the inhibition of GA spontaneous activity caused by the gap junction blocker carbenoxolone. Ajmaline enhances the amplitude of spontaneous contractions in rat gastric and portal vein smooth muscle. This effect may be accompanied, but not caused by an inhibition of enteric neurotransmission. Enhanced syncytial coupling as indicated by its ability to antagonize the effects of carbenoxolone is likely to underlie the enhancement of contractility.
Trace Elements and Electrolytes, 2015
Trace Elements and Electrolytes
Background: To prevent posterior capsule opacification (PCO), we followed the hypothesis that cal... more Background: To prevent posterior capsule opacification (PCO), we followed the hypothesis that calcium channel blockers (antagonists) interfere with integrin signaling and block cell adhesion in lens epithelial cells (LEC). In primary human LEC we found that the T channel antagonist mibefradil induces apoptosis which was accompanied with cell shape changes and loss of cell adhesion. Although T-type calcium channels are substantially present in membranes of freshly dispersed primary cultured hLEC and calcium currents are inhibited by mibefradil at concentrations of 10-8 M, the antiproliferative site of action of this drug remains unclear, since this feature is observed at concentrations 200-fold higher than that for calcium channel blockade. Methods: Epithelial cells of the human lens were dispersed by enzymatic treatment, recordings of membrane currents were performed using patch clamp technique in the whole cell configuration. Westernblot analysis was used for protein detection. Results: Total current elicited on depolarizing voltage steps from a holding potential of-80 mV was composed of inward (calcium) and outward (potassium) current. Outward current could be inhibited mostly by intracellular application of cesium ions. Currents in inward direction were activated fast (< 2 ms) and inactivated during the following 20 ms. They were characterized as calcium currents since the known calcium channel inhibitor nifedipine blocked these currents in a concentration-dependent manner. Using potassium in the pipette (145 mM) as main charge carrier, additionally a noninactivating potassium current and a voltage- and time-dependent potassium current which slowly inactivated (Kv) were observed (control). Adding mibefradil in concentrations from 10-6 M - 10-5 M to the bath solution, the inwardly directed and the non-inactivating current component were inhibited concentration-dependent. The Kv component was affected in a similar way, however, this component showed an increased inactivation behavior after application of mibefradil in the named concentrations. Conclusion: The total effects of mibefradil are significant for the calcium homeostasis since calcium current itself is inhibited but, moreover, the membrane is permanently depolarized up to 20 mV by the drug. Both effects may contribute to the observed reduced cell adhesion during mibefradil treatment. (Less)
Perception, 1985
Apparent motion of a sound source can be induced by a moving visual target. The direction of the ... more Apparent motion of a sound source can be induced by a moving visual target. The direction of the perceived motion of the sound source is the same as that of the visual target, but the subjective velocity of the sound source is 25-50% of that of the visual target measured under the same conditions. Eye tracking of the light target tends to enhance the apparent motion of the sound, but is not a prerequisite for its occurrence. The findings are discussed in connection with the 'visual capture' or 'ventriloquism' effect.
International Journal of Colorectal Disease, 2005
... extended HJ Schrag (*) . F. Fragoza Padilla . UT ... breadth. The following parameters were r... more ... extended HJ Schrag (*) . F. Fragoza Padilla . UT ... breadth. The following parameters were recorded continu-ously during EFS on a three channel pen recorder (Linseis LS 4): the pressure before (Δppm) and inside the smooth muscle ...
The American journal of physiology
The hypothesis that protein kinase C (PKC) is able to regulate the whole cell Ca-activated K (KCa... more The hypothesis that protein kinase C (PKC) is able to regulate the whole cell Ca-activated K (KCa) current independently of PKC effects on local Ca release events was tested using the patch-clamp technique and freshly isolated rat tail artery smooth muscle cells dialyzed with a strongly buffered low-Ca solution. The active diacylglycerol analog 1,2-dioctanoyl-sn-glycerol (DOG) at 10 microM attenuated the current-voltage (I-V) relationship of the KCa current significantly and reduced the KCa current at +70 mV by 70 +/- 4% (n = 14). In contrast, 10 microM DOG after pretreatment of the cells with 1 microM calphostin C or 1 microM PKC inhibitor peptide, selective PKC inhibitors, and 10 microM 1,3-dioctanoyl-sn-glycerol, an inactive diacylglycerol analog, did not significantly alter the KCa current. Furthermore, the catalytic subunit of PKC (PKCC) at 0.1 U/ml attenuated the I-V relationship of the KCa current significantly, reduced the KCa current at +70 mV by 44 +/- 3% (n = 17), and inh...
Autoimmunity Reviews, 2016
Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the... more Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the leading cause of non-traumatic disability among young and middle-aged adults in the western world. One of its most prevalent and debilitating symptoms is fatigue. Despite the general acceptance of the idea of an immune pathogenesis of MS itself, the role of autoimmunity in the course of MS-fatigue is a matter of debate. Both immune-related processes (acute inflammation, chronic inflammation, immune-mediated neurodegeneration, immune-mediated alterations of endocrine functions related to fatigue) and presumably non-immune-mediated disturbances and factors (sleep disturbances, depression, cognitive alterations, chronic infections, adverse effects of medications) contribute to the clinical picture. Data from in vitro and animal experiments has provided evidence for a role of cytokines as IL-1 and TNF-alpha. This association could not be verified directly in blood samples from humans whereas whole blood stimulation protocols gave some indirect evidence for a role of cytokines in MS-fatigue. MRI being able to detect acute and chronic immune mediated damage to the CNS could depict that global atrophy of gray or white matter does not correlate with fatigue. Rather, distinctive clusters of lesions and atrophy at different locations, mostly bifrontal or in subcortical structures, correlate specifically with fatigue. Regardless of the difficulties in pinpointing the immunogenesis of MS-fatigue, an important role of autoimmunity is strongly supported by an indirect route: A growing amount of data shows that the highly effective immunotherapeutics which have been introduced to MS-treatment over the last years effectively and sustainably stabilize and ameliorate fatigue in parallel to their dampening effects on the neuroinflammatory process. This review summarizes the existing data on the relation between inflammation, patterns of CNS-lesions and the effects of immunotherapeutics on MS-fatigue.
Trace Elements and Electrolytes
Trace Elements and Electrolytes, 2014
Trace Elements and Electrolytes, 2014
Trace Elements and Electrolytes, 2014
Cardiovascular Research, 1994
After reviewing recent experimental work from various laboratories we have come to the following ... more After reviewing recent experimental work from various laboratories we have come to the following conclusions. (1) An increase in transmural pressure causes depolarisation of coronary arterioles, which increases smooth muscle tone. Under these conditions the opening of KATP channels can induce a much larger change in membrane potential than in relaxed arteries. Furthermore, the rate of ATP hydrolysis by contractile proteins, and thus the submembrane nucleotide concentrations, might also be changed in the presence of myogenic tone. Therefore care should be taken when extrapolating patch clamp results from isolated coronary smooth muscle cells to the function of KATP channels in vivo. (2) The opening of KATP channels is increased in situations related to energy imbalance, such as hypoxia, adenosine release, intracellular acidification, and lactate accumulation. However, there is increasing evidence that KATP channels also contribute to the setting of the membrane potentials of coronary smooth muscle cells under normoxic conditions. Thus the modulation of KATP channels by intracellular metabolites and by vasoactive autacoids may play an important role in the regulation of coronary blood flow even in the presence of normal intracellular ATP concentrations. (3) The smooth muscle cells of coronary terminal arterioles form an electrical syncytium. The opening of a new KATP channels in smooth muscle cells of a terminal arterioles might induce a spatially homogeneous hyperpolarisation of the entire arteriole. The resulting homogeneous decrease in the tone of the coronary smooth muscle cells of the arteriole may induce a considerable change in vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
British Journal of Pharmacology
1. The effects of NS 1619, the putative BKCa channel opener, were investigated on rat intact port... more 1. The effects of NS 1619, the putative BKCa channel opener, were investigated on rat intact portal veins and on single smooth muscle cells enzymatically separated from the same tissue. 2. Under whole-cell patch clamp conditions with K-rich pipettes, exposure of single cells held at -10 mV to NS 1619 (10-33 microM) induced a noisy, outward current which reached a maximum (33 microM NS 1619; mean 35.8 +/- 17 pA, n = 8) within about 6 min. 3. On stepping to test potentials (range -50 to +50 mV) from a holding potential of -10 mV, the NS 1619-induced noisy current exhibited time-dependent activation and marked outward rectification. 4. The stimulation of outward currents by NS 1619 at -10 mV was independent of the presence of Ca2+ in the bath or pipette solutions but was antagonized by either charybdotoxin (250 nM) or penitrem A (100 nM) in the bath solution. 5. Stationary fluctuation analysis of the noisy current induced by NS 1619 at -10 mV yielded a value of 70 +/- 8 pS (n = 4) (und...
Investigative Ophthalmology & Visual Science, 2016
Nieren- und Hochdruckkrankheiten
Cellular Physiology and Biochemistry
This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 I... more This article is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND). Usage and distribution for commercial purposes as well as any distribution of modified material requires written permission.
Trace Elements and Electrolytes
Pflügers Archiv - European Journal of Physiology
Class-I-antiarrhythmics like ajmaline are known to alter smooth muscle function, which may cause ... more Class-I-antiarrhythmics like ajmaline are known to alter smooth muscle function, which may cause alterations in gastrointestinal motility. The effects of ajmaline on isolated gastric and portal vein smooth muscle and the underlying mechanisms are unknown. We studied the effects of ajmaline on the contractile patterns of isolated preparations of gastric antrum and portal vein from Wistar rats. The organ bath technique was used to measure spontaneous or pharmacologically induced isometric contractions. Changes in force observed after application of ajmaline or under control conditions are reported as % of the amplitude of an initial K +-induced contraction. Electric field stimulation was used to study neurogenic relaxations of gastric fundus smooth muscle. Ajmaline increased the amplitude of spontaneous contractions of muscle strips (portal vein: control 31.1 ± 15.2%, with 100 μM ajmaline 76.6 ± 32.3%, n = 9, p < 0.01; gastric antrum: control 9.5 ± 1.6%, with 100 μM ajmaline 63.9 ± 9.96%, n = 14, p < 0.01). The frequency of spontaneous activity was reduced in portal vein, but not in gastric antrum strips. The effects of ajmaline were not blocked by tetrodotoxin, L-nitroarginine methyl ester, or atropine. Ajmaline abolished coordinated neurogenic relaxations triggered by electric field stimulation and partly reversed the inhibition of GA spontaneous activity caused by the gap junction blocker carbenoxolone. Ajmaline enhances the amplitude of spontaneous contractions in rat gastric and portal vein smooth muscle. This effect may be accompanied, but not caused by an inhibition of enteric neurotransmission. Enhanced syncytial coupling as indicated by its ability to antagonize the effects of carbenoxolone is likely to underlie the enhancement of contractility.
Trace Elements and Electrolytes, 2015
Trace Elements and Electrolytes
Background: To prevent posterior capsule opacification (PCO), we followed the hypothesis that cal... more Background: To prevent posterior capsule opacification (PCO), we followed the hypothesis that calcium channel blockers (antagonists) interfere with integrin signaling and block cell adhesion in lens epithelial cells (LEC). In primary human LEC we found that the T channel antagonist mibefradil induces apoptosis which was accompanied with cell shape changes and loss of cell adhesion. Although T-type calcium channels are substantially present in membranes of freshly dispersed primary cultured hLEC and calcium currents are inhibited by mibefradil at concentrations of 10-8 M, the antiproliferative site of action of this drug remains unclear, since this feature is observed at concentrations 200-fold higher than that for calcium channel blockade. Methods: Epithelial cells of the human lens were dispersed by enzymatic treatment, recordings of membrane currents were performed using patch clamp technique in the whole cell configuration. Westernblot analysis was used for protein detection. Results: Total current elicited on depolarizing voltage steps from a holding potential of-80 mV was composed of inward (calcium) and outward (potassium) current. Outward current could be inhibited mostly by intracellular application of cesium ions. Currents in inward direction were activated fast (< 2 ms) and inactivated during the following 20 ms. They were characterized as calcium currents since the known calcium channel inhibitor nifedipine blocked these currents in a concentration-dependent manner. Using potassium in the pipette (145 mM) as main charge carrier, additionally a noninactivating potassium current and a voltage- and time-dependent potassium current which slowly inactivated (Kv) were observed (control). Adding mibefradil in concentrations from 10-6 M - 10-5 M to the bath solution, the inwardly directed and the non-inactivating current component were inhibited concentration-dependent. The Kv component was affected in a similar way, however, this component showed an increased inactivation behavior after application of mibefradil in the named concentrations. Conclusion: The total effects of mibefradil are significant for the calcium homeostasis since calcium current itself is inhibited but, moreover, the membrane is permanently depolarized up to 20 mV by the drug. Both effects may contribute to the observed reduced cell adhesion during mibefradil treatment. (Less)
Perception, 1985
Apparent motion of a sound source can be induced by a moving visual target. The direction of the ... more Apparent motion of a sound source can be induced by a moving visual target. The direction of the perceived motion of the sound source is the same as that of the visual target, but the subjective velocity of the sound source is 25-50% of that of the visual target measured under the same conditions. Eye tracking of the light target tends to enhance the apparent motion of the sound, but is not a prerequisite for its occurrence. The findings are discussed in connection with the 'visual capture' or 'ventriloquism' effect.
International Journal of Colorectal Disease, 2005
... extended HJ Schrag (*) . F. Fragoza Padilla . UT ... breadth. The following parameters were r... more ... extended HJ Schrag (*) . F. Fragoza Padilla . UT ... breadth. The following parameters were recorded continu-ously during EFS on a three channel pen recorder (Linseis LS 4): the pressure before (Δppm) and inside the smooth muscle ...
The American journal of physiology
The hypothesis that protein kinase C (PKC) is able to regulate the whole cell Ca-activated K (KCa... more The hypothesis that protein kinase C (PKC) is able to regulate the whole cell Ca-activated K (KCa) current independently of PKC effects on local Ca release events was tested using the patch-clamp technique and freshly isolated rat tail artery smooth muscle cells dialyzed with a strongly buffered low-Ca solution. The active diacylglycerol analog 1,2-dioctanoyl-sn-glycerol (DOG) at 10 microM attenuated the current-voltage (I-V) relationship of the KCa current significantly and reduced the KCa current at +70 mV by 70 +/- 4% (n = 14). In contrast, 10 microM DOG after pretreatment of the cells with 1 microM calphostin C or 1 microM PKC inhibitor peptide, selective PKC inhibitors, and 10 microM 1,3-dioctanoyl-sn-glycerol, an inactive diacylglycerol analog, did not significantly alter the KCa current. Furthermore, the catalytic subunit of PKC (PKCC) at 0.1 U/ml attenuated the I-V relationship of the KCa current significantly, reduced the KCa current at +70 mV by 44 +/- 3% (n = 17), and inh...
Autoimmunity Reviews, 2016
Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the... more Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the leading cause of non-traumatic disability among young and middle-aged adults in the western world. One of its most prevalent and debilitating symptoms is fatigue. Despite the general acceptance of the idea of an immune pathogenesis of MS itself, the role of autoimmunity in the course of MS-fatigue is a matter of debate. Both immune-related processes (acute inflammation, chronic inflammation, immune-mediated neurodegeneration, immune-mediated alterations of endocrine functions related to fatigue) and presumably non-immune-mediated disturbances and factors (sleep disturbances, depression, cognitive alterations, chronic infections, adverse effects of medications) contribute to the clinical picture. Data from in vitro and animal experiments has provided evidence for a role of cytokines as IL-1 and TNF-alpha. This association could not be verified directly in blood samples from humans whereas whole blood stimulation protocols gave some indirect evidence for a role of cytokines in MS-fatigue. MRI being able to detect acute and chronic immune mediated damage to the CNS could depict that global atrophy of gray or white matter does not correlate with fatigue. Rather, distinctive clusters of lesions and atrophy at different locations, mostly bifrontal or in subcortical structures, correlate specifically with fatigue. Regardless of the difficulties in pinpointing the immunogenesis of MS-fatigue, an important role of autoimmunity is strongly supported by an indirect route: A growing amount of data shows that the highly effective immunotherapeutics which have been introduced to MS-treatment over the last years effectively and sustainably stabilize and ameliorate fatigue in parallel to their dampening effects on the neuroinflammatory process. This review summarizes the existing data on the relation between inflammation, patterns of CNS-lesions and the effects of immunotherapeutics on MS-fatigue.
Trace Elements and Electrolytes
Trace Elements and Electrolytes, 2014
Trace Elements and Electrolytes, 2014
Trace Elements and Electrolytes, 2014
Cardiovascular Research, 1994
After reviewing recent experimental work from various laboratories we have come to the following ... more After reviewing recent experimental work from various laboratories we have come to the following conclusions. (1) An increase in transmural pressure causes depolarisation of coronary arterioles, which increases smooth muscle tone. Under these conditions the opening of KATP channels can induce a much larger change in membrane potential than in relaxed arteries. Furthermore, the rate of ATP hydrolysis by contractile proteins, and thus the submembrane nucleotide concentrations, might also be changed in the presence of myogenic tone. Therefore care should be taken when extrapolating patch clamp results from isolated coronary smooth muscle cells to the function of KATP channels in vivo. (2) The opening of KATP channels is increased in situations related to energy imbalance, such as hypoxia, adenosine release, intracellular acidification, and lactate accumulation. However, there is increasing evidence that KATP channels also contribute to the setting of the membrane potentials of coronary smooth muscle cells under normoxic conditions. Thus the modulation of KATP channels by intracellular metabolites and by vasoactive autacoids may play an important role in the regulation of coronary blood flow even in the presence of normal intracellular ATP concentrations. (3) The smooth muscle cells of coronary terminal arterioles form an electrical syncytium. The opening of a new KATP channels in smooth muscle cells of a terminal arterioles might induce a spatially homogeneous hyperpolarisation of the entire arteriole. The resulting homogeneous decrease in the tone of the coronary smooth muscle cells of the arteriole may induce a considerable change in vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)
British Journal of Pharmacology
1. The effects of NS 1619, the putative BKCa channel opener, were investigated on rat intact port... more 1. The effects of NS 1619, the putative BKCa channel opener, were investigated on rat intact portal veins and on single smooth muscle cells enzymatically separated from the same tissue. 2. Under whole-cell patch clamp conditions with K-rich pipettes, exposure of single cells held at -10 mV to NS 1619 (10-33 microM) induced a noisy, outward current which reached a maximum (33 microM NS 1619; mean 35.8 +/- 17 pA, n = 8) within about 6 min. 3. On stepping to test potentials (range -50 to +50 mV) from a holding potential of -10 mV, the NS 1619-induced noisy current exhibited time-dependent activation and marked outward rectification. 4. The stimulation of outward currents by NS 1619 at -10 mV was independent of the presence of Ca2+ in the bath or pipette solutions but was antagonized by either charybdotoxin (250 nM) or penitrem A (100 nM) in the bath solution. 5. Stationary fluctuation analysis of the noisy current induced by NS 1619 at -10 mV yielded a value of 70 +/- 8 pS (n = 4) (und...