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R Horn

Publications and source records attributed to R Horn.

At least 127 records · Page 7Linked to original sources

Statistical discrimination of fractal and Markov models of single-channel gating.

A statistical comparison is presented of Markov and fractal models of ion channel gating. The analysis is based on single-channel data from two types of ion channels: open times from a 90 pS Ca-activated K channel from GH3 pituitary cells, and closed times from a nonselective channel from rabbit corneal endothelium (Liebovitch et al., 1987a). Maximum likelihood methods were used to fit the data. For both data sets the best Markov model had three exponential components. The best Markov model had a higher likelihood than the fractal model, and the Asymptotic Information Criterion favored the Markov model for each data set. A more detailed analysis, using the Monte Carlo methods described in Horn (1987), showed that the Markov model was not significantly better than the fractal model for the corneal endothelium channels. The inability to discriminate the models definitively in this case was shown to be due in part to the small size of the data set.

Animals↗

Muscarinic activation of ionic currents measured by a new whole-cell recording method.

A new method is described as an alternative to whole-cell recording in order to prevent "wash-out" of the muscarinic response to acetylcholine (ACh) in rat lacrimal gland cells. The membrane of a cell-attached patch is permeabilized by nystatin in the patch pipette, thus providing electrical continuity between the pipette and the cytoplasm of the cell without the loss or alteration of cytoplasmic compounds necessary for the maintenance of the response to ACh. With normal whole-cell recording in these cells, the response to ACh, seen as the activation of Ca-activated K and Cl currents, lasts for approximately 5 min. With the nystatin method, the response is not diminished after 1 h. Nystatin, applied extracellularly, is shown to cause a rapid and reversible increase of membrane conductance to cations. In the absence of wash-out, we were able to obtain dose-response curves for the effect of ACh on Ca-activated K currents. An increase of [ACh] caused an increase in the K current, with apparent saturation at concentrations above approximately 1 microM ACh. The delay between ACh application and the activation of K current was inversely related to [ACh] and reached a minimum value of 0.7-1.0 s at high [ACh].

Acetylcholine↗

Role of calcium-activated potassium channels in transmitter release at the squid giant synapse.

1. Several compounds known to block Ca2+-activated K+ channels were microinjected into squid 'giant' presynaptic terminals to test the hypothesis that these channels mediate Ca2+-dependent neurotransmitter release. 2. Injection of tetrapentylammonium, nonyl-triethylammonium and decamethonium all reversibly blocked transmission evoked by presynaptic action potentials. 3. All three of these compounds blocked presynaptic Ca2+ channels. The actions of tetrapentylammonium on presynaptic Ca2+ influx were examined in detail and found to be quantitatively sufficient to account for the ability of this compound to inhibit transmitter release. 4. Injection of Ba2+, another agent known to block Ca2+-activated K+ channels, also reversibly blocked evoked transmitter release. Ba2+ simultaneously enhanced basal (asynchronous) transmitter release and thus may be decreasing evoked release by depleting transmitter quanta available for release. 5. None of these results provide any support for the hypothesis that Ca2+-activated K+ channels mediate Ca2+-dependent release of transmitter at the squid synapse. However, our results have identified a new class of compounds that block Ca2+ channels from their cytoplasmic surface.

Animals↗

Crossed cerebello-cerebral diaschisis in a patient with cerebellar infarction.

After supratentorial infarction crossed cerebellar diaschisis has been described. This report concerns the rare phenomenon of crossed cerebral diaschisis in cerebellar infarction. Relative distribution of cerebral and cerebellar blood flow was measured using three-dimensional, qualitative single-photon-emission-computed-tomography (SPECT) with a rotating gamma camera and 123I-IMP. Regional cerebral blood flow was calculated with the two-dimensional, quantitative 133Xe-inhalation-technique. Reduced uptake was observed in the left cerebral hemisphere (-13.9%) contralateral to the cerebellar infarction with the most marked reduction in the left premotor region (-21%). This might be explained by the functional depression of cerebello-ponto-thalamo-cerebral pathways.

Adult↗

Atrial natriuretic peptide and blood pressure in a geographically defined population.

Plasma atrial natriuretic peptide (ANP) was measured in 717 subjects in a cross-sectional study of patients with hypertension (treated and untreated) and normotensive controls, representatives of a geographically defined population. ANP concentrations did not differ between the groups and there was no correlation with blood pressure. These results do not support the view that hypertensive and normotensive subjects have different ANP concentrations; they also call into question the role of ANP in the development of high blood pressure.

Adult↗

Statistical methods for model discrimination. Applications to gating kinetics and permeation of the acetylcholine receptor channel.

Methods are described for discrimination of models of the gating kinetics and permeation of single ionic channels. Both maximum likelihood and regression procedures are discussed. In simple situations, where models are nested, standard hypothesis tests can be used. More commonly, however, non-nested models are of interest, and several procedures are described for model discrimination in these cases, including Monte Carlo methods, which allow the comparison of models at significance levels of choice. As an illustration, the methods are applied to single-channel data from acetylcholine receptor channels.

Ion Channels↗

Disk diffusion susceptibility testing of the Bacteroides fragilis group.

The susceptibilities of 225 isolates of the Bacteroides fragilis group to six antibiotics were determined by a new disk diffusion test in Wilkins-Chalgren agar and by the standard agar dilution method. For disk diffusion, the bacteria were directly suspended in saline and immediately swabbed onto 15-cm agar plates. Disks of cefoxitin (30 micrograms), chloramphenicol (30 micrograms), clindamycin (2 micrograms), moxalactam (30 micrograms), imipenem (10 micrograms), and ticarcillin (75 micrograms) were applied, and the plates were incubated at 37 degrees C in an anaerobic atmosphere. Zone sizes were measured at 24 h. The results of disk diffusion and agar dilution were compared by regression analysis by the method of least squares and by the error rate-bounded method. Zones were easily measured for 216 strains (96%). The correlation between the MICs and diameters of inhibition for cefoxitin, clindamycin, moxalactam, and ticarcillin was generally good. A correlation could not be established for chloramphenicol and imipenem, as there were too few resistant strains. With the recommended resistance breakpoints, the following susceptible and resistant zone diameter breakpoints could be established: cefoxitin, less than or equal to 19 and greater than or equal to 21 mm; clindamycin, less than or equal to 14 and greater than or equal to 18 mm; moxalactam, less than or equal to 21 and greater than or equal to 25 mm; and ticarcillin, less than or equal to 15 and greater than or equal to 16 mm. By applying these zone criteria, the percentage of false-susceptible strains was less than 1% and of false-resistant strains was less than 4% for the drugs tested.

Bacteroides fragilis↗

Isolated muscle cells as a physiological model.

Summary of a symposium presented by the American Physiological Society (Cell and General Physiology Section and Muscle Group) at the 70th Annual Meeting of the Federation of American Societies for Experimental Biology, St. Louis, Missouri, April 15, 1986, chaired by M. Lieberman and F. Fay. This symposium reflects a growing interest in seeking new technologies to study the basic physiological and biophysical properties of cardiac, smooth, and skeletal muscle cells. Recognizing that technical and analytical problems associated with multicellular preparations limit the physiological significance of many experiments, investigators have increasingly focused on efforts to isolate single, functional embryonic, and adult muscle cells. Progress in obtaining physiologically relevant preparations has been both rapid and significant even though problems regarding cell purification and viability are not fully resolved. The symposium draws attention to a broad, though incomplete, range of studies using isolated or cultured muscle cells. Based on the following reports, investigators should be convinced that a variety of experiments can be designed with preparations of isolated cells and those in tissue culture to resolve questions about fundamental physiological properties of muscle cells.

Animals↗

Functional differences between two classes of sodium channels in developing rat skeletal muscle.

Excitability is generated in developing skeletal muscle by the incorporation of sodium-selective ion channels into the surface membrane. Whole-cell and patch voltage-clamp recording from myotubes and their embryologic precursors, myoblasts, indicated that voltage-activated sodium current in myoblasts was more resistant to block by tetrodotoxin (TTX) than that in myotubes. Single-channel recording from both cell types showed two classes of sodium channels. One class had a lower single-channel conductance, activated at more hyperpolarized voltages, and was more resistant to TTX than the other. The proportion of TTX-resistant to TTX-sensitive sodium channels was higher in myoblasts than in myotubes. Thus, the difference in TTX sensitivity between myoblasts and myotubes can be explained by a difference in the proportion of the two classes of sodium channels. In addition, the lower conductance of TTX-resistant channels provides insight into the relationship between the TTX binding site and the external mouth of the sodium channel.

Animals↗

Opentime heterogeneity during bursting of sodium channels in frog skeletal muscle.

Single voltage-activated Na+ channel currents were obtained from membrane patches on internally dialyzed skeletal muscle segments of adult frogs. The high channel density in these membranes permitted frequent observation of the "bursting mode" of individual Na+ channels during 400-ms records. We examined the opentimes within and between bursts on individual membrane patches. We used a new nonparametric statistical procedure to test for heterogeneity in the opentime distributions. We found that although 80% of all bursts consisted of opentimes drawn from a single distribution, the opentime distribution varied significantly from burst to burst. Significant heterogeneity was also detected within the remaining 20% of individual bursts. Our results indicate that the gating kinetics of individual Na+ channels are heterogeneous, and that they may occasionally change in a single channel.

Animals↗

Morphological properties and membrane channels of the growth cones induced in PC12 cells by nerve growth factor.

Large growth cones were produced in vitro by nerve growth factor (NGF) treatment of multinucleate cells produced by chemical fusion of cells of the neuron-like clone PC12. These endings were studied both at the light microscopic and ultrastructural levels. The activity of ionic channels at growth cones was recorded with intracellular microelectrodes, patch recording of single channels, and whole cone recording from mechanically isolated growth cones. Morphologically, these large growth cones were characterized by the presence of microspikes and filopodia, by the presence of actin demonstrated immunohistochemically, and by the presence of catecholamine fluorescence. At the ultrastructural level they contained a broad spectrum of organelles with a distribution characteristic of neuronal growth cones, including dense core vesicles, abundant smooth membrane cisternae, microtubules, and a filamentous network. The presence of channels capable of generating action potentials was revealed by intracellular microelectrode recording from the growth cone in the presence of locally applied tetraethylammonium (TEA). TEA appeared to block outward current channels that could effectively shunt inward current activated by depolarization. Action potentials elicited by depolarizing current in the presence of TEA could be blocked reversibly by Cd2+, a specific blocker of Ca channels. These action potentials were often followed by a long after-hyperpolarization lasting hundreds of milliseconds. This after-hyperpolarization was similar to that recorded in the cell body of PC12 cells where it appears to be mediated by Ca-activated K current. Single channel recording from outside-out excised patches of membrane from the growth cones perfused with KF revealed the presence of voltage sensitive Na channels, Ca-activated K channels, and K channels resembling delayed rectifier K channels. Macroscopic currents recorded from mechanically isolated growth cones in the "whole cone" configuration showed rapid inward currents at potentials greater than or equal to -40 mV, followed by delayed outward currents at more positive potentials, a finding providing additional evidence for the presence of Na and K channels in growth cones.

Adrenal Gland Neoplasms↗

Acute psychosis in a 45-year-old man with bipolar disorder and primary Epstein-Barr virus infection: a case report.

A 45-year-old physician with bipolar disorder presented with an acute organic psychosis, fever, and hematologic and serologic findings of a primary Epstein-Barr virus infection. Pathogenesis was complicated by the history of discontinued lithium therapy prior to the psychosis. The patient recovered completely. Literature concerning psychosis and infectious mononucleosis is reviewed.

Acute Disease↗

Statistical analysis of single sodium channels. Effects of N-bromoacetamide.

Currents were obtained from single sodium channels in outside-out excised patches of membrane from the cell line GH3. The currents were examined in control patches and in patches treated with N- bromoacetamide ( NBA ) to remove inactivation. The single-channel current-voltage relationship was linear over the range -60 to + 10 mV, and was unaffected by NBA . The slope conductance at 9.3 degrees C was 12 pS, and the Q10 for single channel currents was about 1.35. The currents in both control and NBA -treated patches showed evidence of a slow process similar to desensitization in acetylcholine-receptor channels. This process was especially apparent at rapid rates of stimulation (5 Hz), where openings occurred in clusters of records. The clustering of records with and without openings was analyzed by runs analysis, which showed a statistically significant trend toward nonrandom ordering in the responses of channels to voltage pulses. NBA made this nonrandom pattern more apparent. The probability that an individual channel was "hibernating" during an activating depolarization was estimated by a maximum likelihood method. The lifetime of the open state was also estimated by a maximum likelihood method, and was examined as a function of voltage. In control patches the open time was mildly voltage-dependent, showing a maximum at about -50 mV. In NBA -treated patches the open time was greater than in the control case and increased monotonically with depolarization; it asymptotically approached that of the control patches at hyperpolarized potentials. By comparing channel open times in control and NBA -treated patches, we determined beta A and beta I, the rate constants for closing activation gates and fast inactivation gates. Beta I was an exponential function of voltage, increasing e-fold for 34 mV. beta A had the opposite voltage dependence. The probability of an open channel closing its fast inactivation gate, rather than its activation gate, increased linearly with depolarization from -60 to -10 mV. These results indicate that inactivation is inherently voltage dependent.

Acetamides↗