Membrane Channel Interactions Underlying Rat Subthalamic Projection Neuron Rhythmic and Bursting Activity

2006 ◽  
Vol 95 (4) ◽  
pp. 2352-2365 ◽  
Author(s):  
Andrew Gillies ◽  
David Willshaw

A computational model of the rat subthalamic nucleus projection neuron is constructed using electrophysiological and morphological data and a restricted set of channel specifications. The model cell exhibits a wide range of electrophysiological behaviors characteristic of rat subthalamic neurons. It reveals that a key set of three channels play a primary role in distinguishing behaviors: a high-voltage-activated calcium channel (Cav1.2.-1.3), a low-voltage-activated calcium channel (Cav3.-), and a small current calcium-activated potassium channel (KCa2.1–2.3). Short and long posthyperpolarization rebound responses, low-frequency rhythmic bursting (<1 Hz), higher-frequency rhythmic bursting (4–7 Hz), and slow action and depolarizing potentials are behaviors all mediated by the interaction of these channels. This interaction can generate a robust calcium-dependent extended depolarization in the dendrites (a depolarizing plateau). The diversity observed in the rat subthalamic physiology (such as short or long rebounds, or the presence of low-frequency rhythmic busting) can arise from alterations in both the density and distributions of these channel types and, consequently, their ability to generate this depolarizing plateau. A number of important predictions arise from the model. For example, blocking or disrupting the low-voltage-activated Cav3.- calcium current should mute the emergence of rebound responses and rhythmic bursting. Conversely, increasing this channel current via large hyperpolarizing potentials in combination with partial blockade of the high-voltage-activated calcium channels should lead to the more experimentally elusive in vitro high-frequency bursting.

2010 ◽  
Vol 236 (1) ◽  
pp. 81-85 ◽  
Author(s):  
Karolina Čepurnienė ◽  
Paulius Ruzgys ◽  
Rimantas Treinys ◽  
Ingrida Šatkauskienė ◽  
Saulius Šatkauskas

Author(s):  
P. S. Lin ◽  
J. J. Schuler ◽  
A. V. Crewe

A high voltage scanning transmission electron microscope(HVSTEM) has a number of unique features: Compared with a high voltage conventional electron microscope, it can provide better resolution and contrast for thick specimens, because of the absence of the chromatic aberration contributed by energy-loss events; Compared with a low voltage STEM, it can collect inelastically scattered electrons more efficiently, since the the characteristic angle of single inelastic scattering varies inversely with energy; The size of the beam can be varied over a wide range for the purpose of selected-area-diffraction. The application of this promising technique in particular to the study of biological molecules which form crystals too thick to be studied with low voltage electron microscopies awaits exploration. In addition, in theory, the spot size of a HVSTEM is better than one Ångstrom – which undoubtly could not be achieved by a low voltage STEM unless the spherical aberration is corrected.


1998 ◽  
Vol 80 (4) ◽  
pp. 1678-1685 ◽  
Author(s):  
Matthew B. McFarlane ◽  
William F. Gilly

McFarlane, Matthew B. and William F. Gilly. State-dependent nickel block of a high-voltage–activated neuronal calcium channel. J. Neurophysiol. 80: 1678–1685, 1998. Effects of nickel ions (Ni2+) on noninactivating calcium channels in squid giant fiber lobe (GFL) neurons were investigated with whole cell voltage clamp. Three different effects of Ni2+ were observed to be associated with distinct Ca2+ channel activation states. 1) Nickel ions appear to stabilize closed channel states and, as a result, slow activation kinetics. 2) Nickel ions block open channels with little voltage dependence over a wide range of potentials. 3) Block of open channels by Ni2+ becomes more effective during an extended strong depolarization, and this effect is voltage dependent. Recovery from this additional inhibition occurs at intermediate voltages, consistent with the presence of two distinct types of Ni2+ block that we propose correspond to two previously identified open states of the calcium channel. These results, taken together with earlier evidence of state-dependent block by ω-agatoxin IVA, suggest that Ni2+ generates these unique effects in part by interacting differently with the external surface of the GFL calcium channel complex in ways that depend on channel activation state.


1965 ◽  
Vol 208 (5) ◽  
pp. 993-999 ◽  
Author(s):  
S. Katz ◽  
J. H. Perryman

Experiments on cats anesthetized with pentobarbital sodium indicate that a change in the frequency of peripheral nerve stimulation will alter the direction of the blood pressure and respiratory response only after a certain intensity of stimulation is attained. Low voltage-high frequency (1–3 v, 60/sec), high voltage-low frequency (15 v, 10/sec) and low voltage-low frequency stimulation of the tibial and/or peroneal nerves initially produces a decrease in blood pressure (20–50 mm Hg) and a decrease in respiratory minute volume (13–92%). However, high voltage-high frequency stimulation generally produces an increase in blood pressure of 10–65 mm Hg and an 8–14% increase in minute volume. In decerebrate cats, low-voltage, high-frequency as well as high-voltage, high-frequency stimulation of the tibial nerve results in an increase in blood pressure, minute volume, and/or rate and amplitude of phrenic nerve discharge. Frequency and intensity are therefore interrelated. Anatomical specificity of limb peripheral nerve fibers into pressor and depressor afferents is not substantiated.


2019 ◽  
Author(s):  
Dariush Sardari ◽  
Iman Momeni ◽  
Sajad Keshavarz ◽  
Leila Anvari ◽  
Nader Esteeri

Abstract Background The effect of extremely low frequency electric field on cancer cell proliferation is studied in-vitro. Methods Prostate cancer cell culture type Du-145 has been grown in the form of spheroids. It is shown that ELF with 50Hz frequency is effectively suppressing the growth of spheroids and finally reduces their size. Results It is observed that low voltage low frequency electric filed applied for at least 2 hours a day over one week can stop the growth or even reduce the volume of multi-cellular tumor spheroids significantly. No effect for the case of electric field presence in order of 10 -30 minutes per day has been observed.


2022 ◽  
Vol 12 ◽  
Author(s):  
Troels Ronco ◽  
Line H. Kappel ◽  
Maria F. Aragao ◽  
Niccolo Biagi ◽  
Søren Svenningsen ◽  
...  

Multidrug-resistant pathogens constitute a serious global issue and, therefore, novel antimicrobials with new modes of action are urgently needed. Here, we investigated the effect of a phenothiazine derivative (JBC 1847) with high antimicrobial activity on Staphylococcus aureus, using a wide range of in vitro assays, flow cytometry, and RNA transcriptomics. The flow cytometry results showed that JBC 1847 rapidly caused depolarization of the cell membrane, while the macromolecule synthesis inhibition assay showed that the synthesis rates of DNA, RNA, cell wall, and proteins, respectively, were strongly decreased. Transcriptome analysis of S. aureus exposed to sub-inhibitory concentrations of JBC 1847 identified a total of 78 downregulated genes, whereas not a single gene was found to be significantly upregulated. Most importantly, there was downregulation of genes involved in adenosintrifosfat (ATP)-dependent pathways, including histidine biosynthesis, which is likely to correlate with the observed lower level of intracellular ATP in JBC 1847–treated cells. Furthermore, we showed that JBC 1847 is bactericidal against both exponentially growing cells and cells in a stationary growth phase. In conclusion, our results showed that the antimicrobial properties of JBC 1847 were primarily caused by depolarization of the cell membrane resulting in dissipation of the proton motive force (PMF), whereby many essential bacterial processes are affected. JBC 1847 resulted in lowered intracellular levels of ATP followed by decreased macromolecule synthesis rate and downregulation of genes essential for the amino acid metabolism in S. aureus. Bacterial compensatory mechanisms for this proposed multi-target activity of JBC 1847 seem to be limited based on the observed very low frequency of resistance toward the compound.


Author(s):  
T. Miyokawa ◽  
S. Norioka ◽  
S. Goto

Field emission SEMs (FE-SEMs) are becoming popular due to their high resolution needs. In the field of semiconductor product, it is demanded to use the low accelerating voltage FE-SEM to avoid the electron irradiation damage and the electron charging up on samples. However the accelerating voltage of usual SEM with FE-gun is limited until 1 kV, which is not enough small for the present demands, because the virtual source goes far from the tip in lower accelerating voltages. This virtual source position depends on the shape of the electrostatic lens. So, we investigated several types of electrostatic lenses to be applicable to the lower accelerating voltage. In the result, it is found a field emission gun with a conical anode is effectively applied for a wide range of low accelerating voltages.A field emission gun usually consists of a field emission tip (cold cathode) and the Butler type electrostatic lens.


Author(s):  
W. E. King

A side-entry type, helium-temperature specimen stage that has the capability of in-situ electrical-resistivity measurements has been designed and developed for use in the AEI-EM7 1200-kV electron microscope at Argonne National Laboratory. The electrical-resistivity measurements complement the high-voltage electron microscope (HVEM) to yield a unique opportunity to investigate defect production in metals by electron irradiation over a wide range of defect concentrations.A flow cryostat that uses helium gas as a coolant is employed to attain and maintain any specified temperature between 10 and 300 K. The helium gas coolant eliminates the vibrations that arise from boiling liquid helium and the temperature instabilities due to alternating heat-transfer mechanisms in the two-phase temperature regime (4.215 K). Figure 1 shows a schematic view of the liquid/gaseous helium transfer system. A liquid-gas mixture can be used for fast cooldown. The cold tip of the transfer tube is inserted coincident with the tilt axis of the specimen stage, and the end of the coolant flow tube is positioned without contact within the heat exchanger of the copper specimen block (Fig. 2).


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