Histamine release in acute coronary occlusion-reperfusion in isolated guinea-pig heart

It has been shown that plasma histamine significantly increases during myocardial infarction in the dog. Histamine is also released when the isolated guinea-pig heart is reperfused after 30 minutes of low flow perfusion. The release of histamine and lactate dehydrogenase (LDH) after left anterior descending coronary artery ligation and release were investigated in the present study and related to the changes in electrocardiographic parameters and to a computer-aided analysis of left ventricular mast cell metachromasia.Spontaneous release of histamine was unchanged during ischemia and increased after the release of the ligature, while we observed a steady increase of LDH overflow. In parallel, a significant diminution of mast cell granule metachromasia was observed in left ventricular samples.The perfusion of the heart with FeCl₃/ADP (10 M/100M), a free radical-generating system, significantly enhanced both the basal and ischemic-reperfusion release of histamine, while perfusion with N-t-butyl-phenyl-nitrone (BPN/100 M) a spin-trapper molecule, significantly decreased histamine and LDH release and the loss in metachromasia of left ventricular mast cells induced by reperfusion. Inhibitors of xanthine oxidase (allopurinol, 10 M) and of calcium-activated proteases (leupeptin, 10 M) modified the kinetics of histamine and LDH release.     

Cellular localization of inflammatory cytokines in human glomerulonephritis

We evaluated the expression of inflammatory cytokines in renal tissues obtained from 45 patients with several types of glomerulonephritis. Immunofluorescence studies with specific antibodies to interleukin (IL)-1, IL-1, IL-6, tumour necrosis factor (TNF)-, and TNF- showed intense cytoplasmic staining in the glomeruli and interstitium. Cells positive for these cytokines were found frequently in tissue from patients with lupus nephritis (WHO Class IV) and membranoproliferative glomerulonephritis, and, to a lesser extent, in tissue from patients with mesangial proliferative glomerulonephritis, Henoch-Schönlein purpura nephritis, and minimal change nephrotic syndrome. Most of these cells were dual-stained with a monoclonal antibody to monocytes-macrophages. In situ hybridization for cytokine mRNA, combined with immunoperoxidase staining for monocytes-macrophages, detected IL-1, IL-6, and TNF- mRNA in monocytes-macrophages infiltrating the glomeruli and interstitium. Occasionally, there was weak or moderate immunostaining for IL-1, IL-6, and TNF- in the glomerular mesangial and epithelial cells, but in situ hybridization signals were rarely found in these loci. These findings suggest that infiltrating monocytes-macrophages, rather than resident glomerular cells, are the major source of inflammatory cytokines in human glomerulonephritis.     

Erhöhtes atriales natriuretisches Peptid (ANP) bei essentieller Hypertonie — Abhängigkeit vom rechtsatrialen Druckverhalten

Summary The role of atrial natriuretic peptide (ANP) in the pathogenesis of essential hypertension has not yet entirely been clarified. We investigated whether the increase of ANP in essential hypertension may be explained by elevated right atrial pressures and/or a different relationship between right atrial pressures and ANP secretion. Patients with stable essential hypertension undergoing right and left heart catheterization because of suspected coronary heart disease had significantly higher ANP levels than normotensives: 58.7±6.7 pg/ml in hypertensives versus 42.0±4.1 pg/ml in normotensives (p<0,01). Matching hypertensives with normotensives at identical levels of left ventricular enddiastolic pressure revealed significantly higher mean pulmonary artery pressures in hypertensives. Right atrial diastolic pressure (v-wave) after matching for LVEDP was 4.8±0.5 mm Hg in hypertensives and 3.1±0.2 mm Hg in normotensives (p<0.05). In addition, at any given mean right atrial pressure hypertensives showed higher ANP levels than normotensives. These results demonstrate that hypertensives exhibit raised pressures in the pulmonary artery independent of left ventricular pressure load. The elevation in right atrial pressures and the steeper relationship between these pressures and ANP are a suitable explanation for raised ANP levels in hypertension. ANP in essential hypertension may represent a counterregulation against elevated pulmonary resistance.

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Abkürzungsverzeichnis ANP Atriales natriuretisches Peptid - LVEDP Left ventricular enddiastolic pressure (Linksventrikulärer enddiastolischer Druck) - RAO Right anterior oblique (Aufnahmetechnik von rechter schräger Bildröhrenposition aus) - SEM Standard estimate of the mean (Standardabweichung dividiert durch die Wurzel aus der Fallzahl) - HT Hypertoniker - NT Normotoniker Mit Unterstützung der Deutschen Forschungsgemeinschaft     

A comparative immunohistological study of cerebellar enolases

Summary A comparative immunohistological study of the neurone-specific enolase and enolase, demonstrates the exclusive neuronal localization of enolase and its absence from glial cells. In contrast, enolase is located in astroglial cells. The validity of enolase as a neuronal marker and enolase as an astrocytic marker, is confirmed both by a double labelling technique, using antibodies to and to revealed with fluorescence or peroxidase in the same tissue sections, and by immunoelectronmicroscopy.     

Restricted Vβ gene usage of tumour-infiltrating T lymphocytes in primary gastric malignant B-cell lymphoma

Ten cases of primary gastric malignant lymphoma (PGL) were investigated by immunohistochemical and molecular genetic analysis. These cases were diagnosed histopathologically as follicular small cleaved cell type (1 case), diffuse small cleaved cell type (3 cases) and diffuse large cell type (6 cases) based on the WF (Working Formulation) classification. Seven cases classified as small cleaved or diffuse large cell type belong to low (4 cases) or high (3 cases) grade MALT lymphoma according to Isaacson's classification. All PGL belonged to B lineage cells according to immunohistochemical study and immunoglobulin rearrangements. Rearrangements of TCR chain genes were observed in four of the ten cases. The possibility that the TCR rearrangements were caused by tumour-infiltrating T-cells (TILs) was supported by the following observations: the tumours did not show T- and B-cell biphenotype, TCR exhibited functional VDJ rearrangement and V usage pattern was not a neoplastic type. Analysis of the repertoire of the TCR chain in TILs revealed a common usage of V2 in the above four cases, and furthermore, predominant usage of a particular chain composed of V2-D2.1-J2.3 was observed in one of the four cases. These results indicate that the TILs of PGL have a restricted TCR repertoire.     

The great cardiac vein

Summary The great cardiac vein is the longest venous vessel of the heart; in the majority of our cases it originated at the lower third of the anterior interventricular sulcus (58%). The great and the middle cardiac veins merge at the apex of the heart, forming together with the coronary sinus into which they both empty, a complete venous ring around the left ventricle (13%). On reaching the area of the coronary sulcus, the great cardiac vein crosses the anterior interventricular branch and the circumflex branch of the left coronary artery forming the triangle of Brocq and Mouchet in which the vein is mainly superficial (61%). One, two or three anterior ventricular branches of the left coronary artery traverse this triangle; the relations of the vein and these arteries are very variable and practically unpredictable in 30% of the cases.

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La grande veine du cur

Résumé La grande v. du cur est le plus long vaisseau du cur. Dans la majorité des cas que nous avons étudié, elle prend son origine au tiers inférieur du sillon inter-ventriculaire antérieur (58%). Les grandes et moyennes v. du cur confluent au sommet du cur réalisant, avec le sinus coronaire dans lequel elles se drainent, un anneau veineux complet autour du ventricule gauche (13%). Pour atteindre le haut du sillon coronaire, la grande v. du cur croise la branche inter-ventriculaire antérieure et la branche circonflexe de l'a. coronaire gauche délimitant ainsi le triangle de Brocq et Mouchet où la veine est le plus souvent superficielle. Ce triangle est traversé par une, deux ou trois branches ventriculaires antérieures de l'a. coronaire gauche. Les relations de cette veine avec ces artères sont très variables et en fait imprévisibles dans 30 % des cas.

     

Neuron Activity in the Prefrontal Cortex of the Brain in Rats with Different Typological Characteristics in Conditions of Emotional Stimulation

Male Wistar rats were separated according to the emotional resonance method (groups of animals avoiding (altruists) and not avoiding (egotists) the pain cries of partner rats) and neuron activity in the prefrontal areas of the cortex was studied in the right and left hemispheres. Assessments were made of changes in the frequency of nerve cell spike activity (in relation to the baseline activity of neurons in sated animals) in rats subjected to one day of food deprivation and after electrical stimulation of emotionally positive (lateral hypothalamus) and negative (tegmentum of the midbrain) brain structures and after exposure to the pain cries of partner rats. The results of these experiments revealed a series of differences in the cell activities of the two groups of rats. In conditions of hunger, the discharge frequency in the altruists was higher than that in egotists. Cortical neuron responses to positive stimulation were greater than those to negative stimulation in rats of both groups. Intracerebral stimulation produced significantly greater increases in discharge frequency in neurons of both prefrontal areas of the cortex in altruists than in egotists. In both groups of rats, neurons in the right hemisphere responded to emotionally negative stimulation with significantly greater activation than cells in the left hemisphere, while activity in the left hemisphere was greater in conditions of emotionally positive stimulation. Altruists showed significantly greater neuron responses during exposure to pain cries from victim rats in both the right and left hemispheres. The responses of egotists to victim cries were not significantly different from baseline activity levels.     

Sensitivity to dihydropyridines, ω-conotoxin and noradrenaline reveals multiple high-voltage-activated Ca2+ channels in rat insulinoma and human pancreatic β-cells

High-voltage-activated (HVA) Ba²⁺ currents of rat insulinoma (RINm5F) and human pancreatic -cells were tested for their sensitivity to dihydropyridines (DHPs), -conotoxin (-CgTx) and noradrenaline. In RINm5F cells, block of HVA currents by nimodipine, nitrendipine and nifedipine was voltage- and dose-dependent (apparent K _D<37 nM) and largely incomplete even at saturating doses of DHPs (mean 53%, at 10 M and 0 mV). Analysis of slow tail currents in Bay K 8644-treated cells indicated the existence of Bay K 8644-insensitive channels that turned on at slightly more positive voltages and deactivated more quickly than Bay K 8644-modified channels. DHP Ca²⁺ agonists and antagonists in human -cells had similar features to RINm5F cells except that DHP block was more pronounced (76%, at 10 M and 0 mV) and Bay K 8644 action was more effective, suggesting a higher density of L-type Ca²⁺ channels in these cells. In RINm5F cells, but not in human -cells, DHP-resistant currents were sensitive to -CgTx. The toxin depressed 10–20% of the DHP-resistant currents sparing a residual current (25–35%) with similar voltage-dependent characteristics and Ca²⁺/Ba²⁺ permeability. Noradrenaline (10 M) exhibited different actions on the various HVA current components: (1) it prolonged the activation kinetics of -CgTx-sensitive currents, (2) it depressed by about 20% the size of DHP-sensitive currents, and (3) it had little or no effects on the residual DHP- and -CgTx-resistant current although intracellularly applied guanosine 5-O-(3-thiotriphosphate) (GTP--S) prolonged its activation time course. The first action was clearly voltage-dependent and most evident in RINm5F cells that displayed neuronal-like processes. The second was observed more frequently, was voltage-independent and fully blocked by saturating doses of nifedipine (10 M). Both actions were prevented by intracellular perfusion with guanosine 5-O-(2-thiodiphosphate) (GDP--S). Our data suggest that beside a majority of L-type channels, RINm5F and human pancreatic -cells may express a variable fraction of DHP-insensitive channels that may be involved in the control of insulin secretion during -cell activity.     

Interferon β1a Treatment Modulates TH1 Expression in γδ + T Cells from Relapsing-Remitting Multiple Sclerosis Patients

A paradigm exists that multiple sclerosis is causally related to dysregulation of T_H1 inflammatory cytokines and T_H2 antiinflammatory cytokines. The cytokine source(s) that initiate the imbalances are unknown. In this study, , CD4, and CD8 T cell receptor-positive (TCR+) cells were isolated from the blood of 26 definitive relapsing-remitting multiple sclerosis patients prior to interferon -1a (IFN1a) therapy and following 8–10 weeks of this therapy. The bioactivities of interferon (IFN), interleukin 10 (IL10), and interleukin 12 (IL12) were determined. The concentrations of IFN, IL10, and IL12 from each cell type did not change significantly with IFN1a treatment. The IL10 secreted by TCR+ cells strongly correlated with the IL12 secreted by the same TCR+ cells, supporting the paradigm. Furthermore, IFN1a therapy decreased the TCR+ cell secretion of T_H1 cytokines after 8–10 weeks of therapy.     

Interferon-γ for treatment of severe atopic eczema in two children

Two 4- and 5-year-old children suffering from refractory atopic dermatitis were treated with recombinant interferon- (rIFN-). rIFN- was injected at 50 g subcutaneously three times a week in the first child for 3 weeks, followed by three times 25 g in week 4. In the other child two treatment courses of 4 weeks were given after a break of 2 weeks. Therapy was well tolerated. In child one reductions in eczematous body surface and severity of lesions were observed, while no beneficial effect was seen in the other. Clinical chemistry data remained unchanged. Immunological studies performed in parallel showed a decrease in total serum IgE of 50% in child 1, a decrease in spontaneous in vitro IgE production, an increase in in vitro production of interleukin-6, and a normalization of previously decreased in vitro lymphocyte responses to several mitogens. While marked immunological changes were noted during IFN- treatment, clinical benefits were not encouraging. Diminished IFN- production has been claimed to be a major pathogenic factor in atopic eczema. Our results indicate that the pathogenesis is more complex. Clinically, we were unable to confirm previous observations in adults. Further studies are needed before IFN- can be recommended for therapy of pediatric atopic eczema.Abbreviations IFN- interferon- - IL interleukin     

Analysis of Cyclic Adenosine-3',5'-Monophosphate Levels in Structures of the “Informational” and “Motivational” Systems of the Rat Brain during Acquisition of a Conditioned Active Avoidance Reaction

Cyclic adenosine-3',5'-monophosphate (cAMP) levels in structures of the informational and motivational systems of the brain were measured during acquisition of a conditioned two-sided active avoidance reflex in rats. cAMP levels were measured in three groups of animals – intact animals, trained animals, and an active control group (given uncombined presentations of the conditioned (light) and unconditioned (electric shock) stimuli) – immediately after reproduction of the acquired reflex. Significant accumulation of cAMP levels in brain structures was seen in animals of the active control group in the hypothalamus and in trained animals in the left and right hippocampus and the right frontal cortex. Positive correlations were found between cAMP levels in symmetrical parts of the frontal cortex, amygdala, and hypothalamus in animals of all study groups. In addition, active control rats and trained rats showed interhemisphere and intrahemisphere correlations between cAMP levels in brain macrostructures, whose patterns were specific for each group. The pattern of correlations observed here is assessed from the point of view of the role of the informational and motivational structures in the organization of adaptive behavior.     

Coronarvasomotorik unter l-Noradrenalin und Isopropylnoradrenalin nach Blockierung der adrenergischen β-Receptoren durch Nethalide

1. The left coronary artery (ramus descendens or circumflexus) was cannulated and perfused with constant pressure. Phasic blood flow was measured by an electromagnetic This method allowed estimation of vasomotor activity within the coronary bed by means of recording enddiastolic blood flow.2. Marked dilations of perfused coronary vessels were caused by intracoronary infusions of isoproterenol as well as noradrenaline.3. Intravenous administration of the -receptor-blocking agent Nethalide was accompanied by a reduction in enddiastolic flow.4. After blocking the -receptors, the isoproterenol induced dilation of coronary vessels was greatly diminished, whereas noradrenaline now led to vasoconstriction.5. The results suggest that -receptors exist within the coronary bed. Noradrenaline has a dual coronary vasomotor action: the constrictory effect (mediated by -receptors) is normally exceeded by the greater dilatory effect (mediated by -receptors). Because of its dual influence it is believed that under physiological conditions Noradrenaline takes part in regulation of coronary vasomotor tone.

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Mit 4 Textabbildungen

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Vorläufige Ergebnisse wurden auf der 29. Tagung der Deutschen Physiol. Gesellschaft in Bad Nauheim vorgetragen⁷.     

Differential effects of interleukin-1α and β on the arachidonic acid cascade in human synovial cells and chondrocytes in culture

The effects of interleukin-1 and were tested on the [³H]-arachidonic acid release and the prostaglandin synthesis by human cultured synovial cells and chondrocytes. Both forms of interleukin-1 stimulated the arachidonic acid release but interleukin-1 was more potent than IL-1. Human synovial cells and chondrocytes synthesized three types of prostaglandins upon stimulation with interleukin-1 or : prostaglandin E₂, F₂ and 6-keto-prostaglandin F₁. Regarding the synthesis of these prostaglandins, IL-1 was again more potent than IL-1. A comparison between interleukin-1-stimulated synovial cells and chondrocytes revealed neither significant quantitative nor qualitative differences in both the arachidonic acid release and the prostaglandin synthesis.     

Effects of vector cutting on its recombination with the chromosomal immunoglobulin gene in hybridoma cells

We have analyzed the effects of linearizing vector DNA on the frequency and pathway of its recombination with the homologous chromosomal gene. The pSV2neo vector bearing a 4.3-kb fragment encoding the mouse immunoglobulin heavy chain constant (C) region was cut either at sites within the C segment or outside C and then transferred to hybridoma cells bearing a mutant gene. The frequency of recombinant cells producing normal was then measured. For most cut sites, whether in regions of homology or of nonhomology, linearization of the transferred DNA enhanced the recombination frequency between the vector and chromosomal genes. When the vector was either uncut or cut at SacI in the region of homology, G418-resistant m⁺ recombinants were found to have integrated the vector by a single reciprocal homologous crossover; the enzyme site (SacI) used for cutting was present in the recombinants. By contrast, when the vector had been linearized at Pvul or SfiI in the region of nonhomology, vector integration involved nonhomologous crossovers, either between transferred DNA molecules or between transferred and chromosomal DNA, and the vector cut sites were absent in these recombinants. Some recombinants were found to have an unaltered as well as recombinant gene, suggesting that the nonhomologous recombination process might have involved sister chromatids.     

Effect of noradrenalin on the collateral coronary circulation

Summary A study was made of the action of noradrenalin (in doses of 0.5 g/kg and 4 g/kg) on collateral coronary circulation of dogs. Administration of g/kg caused a brief increase in the retrograde coronary flow in direct proportion to its pressor effect. Low doses of noradrenalin induced stable increase in the retrograde blood flow in the descending branch of the left coronary artery against the background of the normalized general blood pressure.(Presented by Active Member AMN SSSR V. A. Sanotskii) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 58, No. 8, pp. 72–74, August, 1964     

Relations between axons and oligodendroglial cells during initial myelination. II. The individual axon

Summary Axo-glial relations in the ventral funiculus of the spinal cord (SC) and in the corpus callosum (CC) of the cat were examined by electron microscopy during initial myelination. In addition to random transverse and longitudinal sections from several stages, two series of sections were studied. As a first step in myelination the axons become ensheathed by one to three uncompacted glial lamellae (E-sheaths). E-sheaths present a length range from <5 m to 149 m (SC) or to 93 m (CC). E-sheaths are more frequent along SC-axons than CC-axons, and the mean E-sheath is 3.3-fold longer in the former compared to the latter. In both areas naked axon portions occur between successive E-sheaths, but these gaps are insufficient to allow elongation of all short E-sheaths into long ones. Sheaths composed of mixed compacted (M-sheaths) and uncompacted segments have a length range of 66–212 m in the SC and 66–171 m in the CC. In relation to the undifferentiated terminations of E-sheaths or mixed E/M-sheaths, undercoated axolemmal domains are always lacking. Fully compacted sheaths were not found in the series from the SC. In the CC, 141–212 m long compact sheaths were found, with tight axoglial junctions at their terminations. Axolemmal domains with a nodal undercoating occur in relation to some of these terminations. In both areas, individual developing axons present a chaotic mixture of naked, ensheathed and myelinated portions; bulges with clusters of vesiculotubular profiles are frequent along naked and ensheathed axonal portions, particularly in the SC. The axon diameter is clearly larger in myelinated than in naked portions of the same axon. On the basis of these results, we propose that the early glial sheaths of developing CNS axons actively elongate and undergo extensive remodelling before compaction. The maximal length of uncompacted E-sheaths, and the sheath length at which axoglial junctions and nodes of Ranvier form, are markedly different in the two areas.     

Interaction of G-actin with thymosin β4 and its variants thymosin β9 and thymosin β 9 met

Summary Thymosin ₄ is a major actin sequestering peptide in vertebrate cells and plays a role in the regulation of actin monomer/polymer ratio. Thymosin ₉ and thymosin ₉ ^met are minor variants of thymosin ₄. The possible function of these peptides has been investigated by comparing the actin binding properties of these -thymosins. Thymosin ₉ and thymosin ₉ ^met were found to inhibit polymerization of ATP-actin with identical K _d s of 0.7–0.8 M (as compared to 2±0.3 M for thymosin ₄); like thymosin ₄, they bound to ADP-G-actin with a 100-fold lower affinity than to ATP-G-actin. The interaction of thymosin ₄ and thymosin ₉ ^met with G-actin was weakened 20-fold upon oxidation of methionine-6 into methionine sulfoxide. Binding of thymosin ₄ to G-actin was accompanied by a 15% increase in the fluorescence intensity of actin tryptophans, and a 10 nm emission blue shift. Methionine-6 played an important role in this effect. The fluorescence change was used to monitor the kinetics of thymosin ₄ binding to G-actin in the stopped-flow. The reaction was bimolecular, with association and dissociation rate constants of 1.5 M^-1 s^-1 and 2s^-1 respectively, under physiological conditions. The possible physiological significances of methionine-6 oxidation and of the relatively slow binding kinetics in regulating thymosin ₄ function in vivo is discussed.     

Altered synthesis of interferon-γ and expression of interferon-γ receptor by peripheral blood mononuclear cells from patients with IgA nephropathy and non-IgA proliferative glomerulonephritis

Previously we reported disease-specific interaction between interferon- (IFN-) and interleukin-4 (IL-4) in patients with IgA nephropathy (IgAN), suggesting the existence of unusual T cell behavior in this disease. In the present study, we investigated characteristic synthesis of interferon- (IFN-) and expression of IFN- receptor (IFN-R) in the peripheral blood mononuclear cells (PBMC) from patients with IgAN and other chronic proliferative glomerulonephritis (PGN). Heparinized peripheral blood samples were obtained from 38 patients with chronic mesangial proliferative glomerulonephritis (CGN; including 24 with IgA nephropathy) and 20 healthy controls. PBMC were isolated by gradient centrifugation and fragments were cultured in Iscove's modified Dulbecco's medium (IMDM) supplemented with 10% fetal calf serum (FCS) for 72 hr. IFN- concentrations in supernatants were evaluated by the enzyme-linked immunosorbent assay (ELISA). Other parts of PBMC pellets were reacted with anti-human IFN-R monoclonal antibody and FITC-labeled anti-mouse second antibody for analysis of IFN-R expression on these cells by FACScan. The remaining PBMC were fractionated into CD4⁺ T cells, CD8⁺ T cells, B cells, NK, cells and macrophages using the MACS cell sorting system. The isolated cells were evaluated for IFN- or IFN-R mRNA expression by the semiquantitative RT-PCR method.In vitro IFN- synthesis was enhanced in patients with CGN, and NK cells were revealed to be responsible for such enhancement. On the other hand, the expression of IFN-R on macrophages was suppressed in CGN patients. These results suggest that impairment of regulation of the IFN- system might be involved in the development of CGN.     

Immunological study of HB-Ag carriers

Summary The serum immunoglobulin levels, the presence of circulating autoantibodies, the number of peripheral atypical lymphocytes and the number of DNA and RNA synthesizing mononuclear cells were studied in a group of healthy HB-Ag (australia Antigen) carriers and in a group of healthy HB-Ag negative control subjects.In the HB-Ag carriers, in spite of the persistent antigenaemia, all these immunological findings were normal (as in the control subjects).     

Tedisamil blocks single large-conductance Ca2+-activated K+ channels in membrane patches from smooth muscle cells of the guinea-pig portal vein

Enzymatically dispersed smooth muscle cells of the guinea-pig portal vein were studied by the patch-clamp technique. They were found to have Ca²⁺-dependent K⁺ channels with the typical properties of the BK channel, i.e. a reversal potential at the calculated equilibrium potential for K⁺ ions, a striking voltage dependence, and a conductance of approximately 200 pS ([K⁺]₀ 50 mM, [K⁺]_i 150 mM, positive patch potentials). Tedisamil, a new bradycardic agent with an inhibitory action on K⁺ currents in heart muscle, reduced the open probability of the BK channels concentration-dependently (1–100 M) when applied at the cytosolic side of membrane inside-out patches. At 100 M [Ca²⁺]_i, the IC₅₀ of tedisamil was 13.8 M (¯x, n=5). Tedisamil increased the frequency of channel closures, and reduced the mean duration of openings from 8 ms to < 1 ms, while the mean duration of closures within bursts (1–2 ms) was not altered. Tedisamil did not affect long closures (> 160 ms) between bursts, either. The mean time of residence of tedisamil at the BK channel was estimated to be 1–2ms. Hence, tedisamil, in comparison to the slow blocker Ba²⁺ and the fast blocker tetraethylammonium, holds the position of an intermediate K⁺ channel blocker.Supported by the Deutsche Forschungsgemeinschaft