1,720,976 research outputs found
MODIFICATIONS OF A-CURRENT KINETICS IN MAMMALIAN CENTRAL NEURONS INDUCED BY EXTRACELLULAR ZINC
No full text1. Whole-cell voltage clamp recordings were used to study the action of the transition ion zinc on the A-current kinetics in granule cells from rat cerebellar slices. 2. The effects of zinc have been tested in the concentration range from 1 mu M to 1 mM, and fully characterized on all kinetic parameters at 100 and 300 mu M. All the effects observed were rapid, concentration dependent and fully reversible. 3. Steady-state inactivation curves are strongly shifted towards depolarized potentials, with activation curves much less so. These shifts lead to an increase of the peak current amplitude around physiological resting membrane potentials and to a decrease at hyperpolarized potentials. 4. The forward 'on' rate constants are slowed by Zn2+ at a concentration of 100-300 mu M by a factor from 1.5 to 4. The backward 'off' rate constants are unaffected by Zn2+. 5. The development of I-A inactivation, as measured from the current decay, is not affected by Zn2+ up to 1 mM. Removal of inactivation is, on the contrary, significantly slowed. 6. The results are neither compatible with the theory of the surface charge screening effect nor with a mechanism involving channel block. It seems more likely that Zn2+ interferes with the channel gating by binding to a specific domain of the channel protein. 7. After treatment with Hg2+, which is irreversible, Zn2+ still maintains its effects, which suggest that the two divalents act at different sites. 8. In view of the widespread distribution of zinc throughout the brain, its actions on the A-current could play an important role in physiological function
Identification of delayed potassium and calcium currents in the rat sympathetic neurone under voltage clamp
No full textPost-ganglionic neurones of the isolated rat superior cervical ganglion were studied at 37 degrees C under two-electrode voltage-clamp conditions. Membrane depolarization beyond -40 mV from holding levels between -50 and -100 mV produced a delayed outward current which exhibited no inactivation within this voltage range. The current is carried primarily by K+ ions and its instantaneous I-V relation is linear. The total outward current could be separated into two distinct components on the basis of ion-substitution experiments. A voltage-dependent component of the delayed current, termed IK(V), is activated by membrane depolarization beyond -40 mV when Ca2+ fluxes are selectively blocked by Cd2+ or in Ca2+-free solution. IK(V) develops following first-order kinetics and rises to a peak with a voltage-dependent delay (239 ms at -30 mV and 23 ms at +10 mV). GK(V) attains a saturating value of the order of 17 mS/cm2 at about +20 mV and can be described in terms of a simple Boltzmann distribution for a single gating particle with a valency equal to +2.5. A second component of the delayed outward current, termed IK(Ca), depends on Ca2+ entry for its activation and was isolated as difference current before and after block of Ca2+ movements across the membrane. IK(Ca) is larger and faster than IK(V): it is strictly related to Ca2+ influx and also depends on membrane potential depolarization. A distinct Ca2+ current, ICa, was recorded from the neurone exposed to Na+-free or tetrodotoxin solution. ICa was activated by membrane depolarization beyond -30 mV and reached a maximum value near 0 mV. Its activation agrees with fourth-order kinetics and becomes faster with increasing depolarization. The Ca2+ current developed with a voltage-dependent time to peak of 2.9-1.8 ms and thereafter completely inactivated. The relationship between ICa and IK(Ca) is discussed. The Ca2+-k+ repolarizing system is expected to be mainly associated with action potentials arising from a depolarized neurone, whereas the IA current (Belluzzi, Sacchi & Wanke, 1985) dominates the repolarization mechanism at the normal membrane potential. The effect of muscarine was examined. Muscarine (10-50 microM) produced a fall in conductance with a voltage dependence similar to that exhibited by GK(Ca) and was ineffective when removing extracellular Ca2+ or adding Cd2+. A partial suppression of ICa by muscarine is demonstrated. It is suggested that the decrease of the outward current magnitude in the presence of muscarine may be accounted for qualitatively by the reduction in ICa
A quantitative description of the sodium current in the rat sympathetic neurone.
No full textThe somata of rat sympathetic neurones were voltage-clamped in vitro at 27 degrees C using separate intracellular voltage and current micro-electrodes. Na currents were isolated from other current contributions by using: Cd to block the Ca current (ICa) and the related Ca-dependent K current (IK(Ca)), and external tetraethylammonium to suppress the delayed rectifier current (IK(V) ). The holding potential was maintained at -50 mV to inactivate the fast transient K current (IA) when the IA contamination was unacceptable. Step depolarizations beyond -30 mV activated a fast, transient inward current carried by Na ions; it was suppressed by tetrodotoxin and was absent in Na-free solution. Once activated, INa declined exponentially to zero with a voltage-dependent time constant. The underlying conductance, gNa, showed a sigmoidal activation between -30 and +10 mV, with half-activation at -21.1 mV and a maximal value (mean gNa) of 4.44 microS per neurone. The steady-state inactivation level, h infinity, varied with membrane potential, ranging from complete inactivation at -30 mV to minimal inactivation at about -90 mV with a midpoint at -56.2 mV. Double-pulse experiments showed that development and removal of inactivation followed a single-exponential time course; tau h was markedly voltage-dependent and ranged from 46 ms at -50 mV to 2.5 ms at -100 mV. Besides the fast inactivation, the Na conductance showed a slow component of inactivation. The steady-state value, s infinity, was maximal at -80 mV and minimal at -40 mV. The removal of slow inactivation is a two-time-constant process, the first with a time constant in the order of hundreds of milliseconds and the second with a time constant of seconds. Slow inactivation onset appeared to be a faster process than its removal. When slow inactivation was fully removed the peak INa increased by a factor of 1.8. INa was well described by assuming it to be proportional to m3h. The temperature dependence of peak INa, tau m and tau h was studied in the temperature range 17-27 degrees C and found similar to that reported for other preparations. The Q10 of these parameters allowed the reconstruction of the INa kinetic properties at 37 degrees C
Inward rectifier potassium (Kir) current in dopaminergic periglomerular neurons of the mouse olfactory bulb.
No full textDopaminergic (DA) periglomerular (PG) neurons are critically placed at the entry of the bulbar circuitry, directly in contact with both the terminals of olfactory sensory neurons and the apical dendrites of projection neurons; they are autorhythmic and are the target of numerous terminals releasing a variety of neurotransmitters. Despite the centrality of their position, suggesting a critical role in the sensory processing, their properties -and consequently their function- remain elusive. The current mediated by inward rectifier potassium (Kir) channels in DA-PG cells was recorded by adopting the perforated-patch configuration in thin slices; IKir could be distinguished from the hyperpolarization-activated current (I h ) by showing full activation in <10 ms, no inactivation, suppression by Ba(2+) in a typical voltage-dependent manner (IC50 208 μM) and reversal potential nearly coincident with EK. Ba(2+) (2 mM) induces a large depolarization of DA-PG cells, paralleled by an increase of the input resistance, leading to a block of the spontaneous activity, but the Kir current is not an essential component of the pacemaker machinery. The Kir current is negatively modulated by intracellular cAMP, as shown by a decrease of its amplitude induced by forskolin or 8Br-cAMP. We have also tested the neuromodulatory effects of the activation of several metabotropic receptors known to be present on these cells, showing that the current can be modulated by a multiplicity of pathways, whose activation in some case increases the amplitude of the current, as can be observed with agonists of D2, muscarinic, and GABAA receptors, whereas in other cases has the opposite effect, as it can be observed with agonists of α1 noradrenergic, 5-HT and histamine receptors. These characteristics of the Kir currents provide the basis for an unexpected plasticity of DA-PG cell function, making them potentially capable to reconfigure the bulbar network to allow a better flexibility
ELECTROPHYSIOLOGICAL EFFECTS OF A NEUROTOXIN EXTRACTED FROM THE SKIN OF THE AUSTRALIAN FROG PSEUDOPHRYNE-CORIACEA
No full text1. The electrophysiological effects of a pumiliotoxin-B-like alkaloid extracted from the skin of the Australian frog Pseudophryine coriacea (PsC) have been studied in rat superior cervical ganglia at 37-degrees-C. 2. PsC (50 mg/ml) elicits a broadening of the evoked compound action potential and, at rest, the appearance of spontaneous spike discharge at 10-20 Hz. Action potentials presumably originate far away from the soma, which is invaded in a typical IS-SD sequence. 3. The toxin effect is not related to any direct action on the preganglionic fibers of the sympathetic trunk, and does not involve synaptic mechanisms. 4. Two-electrode voltage-clamp experiments showed that the main properties of the major voltage-dependent ionic currents are apparently unaffected by the toxin, while the cell input resistance is considerably reduced. 5. The data are consistent with the hypothesis that PsC elicits a cationic permeability increase generating a pacemaker current in a region close to the cell soma
Metabotropic glutamate receptors 1 and 5 differentially regulate bulbar dopaminergic cell function
No full textEffects of activation of metabotropic glutamatergic receptors (mGluR) were investigated in mouse dopaminergic olfactory bulb neurons. After blockage of ionotropic receptors, focal application of glutamate or of group I/II mGluR agonist t-ACPD resulted in a depolarization, paralleled by an inward current in voltage-clamp conditions. The Group I agonist DHPG induced a depolarization, which could be largely blocked by mGluR1 antagonists. The DHPG action i) was prevented by buffering intracellular Ca2+ with BAPTA and by a phospholipase C inhibitor; ii) was not affected by the block of Ca2+ entry, and iii) was blocked by inhibitors of the Na+/Ca2+ exchanger. These observations were interpreted as a mGluR1-mediated intracellular Ca2+ release, followed by the activation of an electrogenic Na+/Ca2+ exchanger. The mGluR5 agonist CHPG induced a hyperpolarization of membrane potential, resulting in a decrease of the spontaneous firing frequency. CHPG induced i) a decrease in membrane resistance; ii) an increase in the action potential repolarization rate, and iii) an increase in the amplitude of the afterhyperpolarization. This was interpreted as a mGluR5-mediated opening of a K+ conductance. These data suggest that mGluR1 and mGluR5 play different and non-overlapping roles in the regulation of the excitability of bulbar dopaminergic neurons. © 2010 Elsevier B.V. All rights reserved
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
- …
