State-Dependent Nickel Block of a High-Voltage–Activated Neuronal Calcium Channel

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.

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.


2016 ◽  
Vol 147 (6) ◽  
pp. 497-505 ◽  
Author(s):  
Conor McClenaghan ◽  
Marcus Schewe ◽  
Prafulla Aryal ◽  
Elisabeth P. Carpenter ◽  
Thomas Baukrowitz ◽  
...  

The TREK subfamily of two-pore domain (K2P) K+ channels exhibit polymodal gating by a wide range of physical and chemical stimuli. Crystal structures now exist for these channels in two main states referred to as the “up” and “down” conformations. However, recent studies have resulted in contradictory and mutually exclusive conclusions about the functional (i.e., conductive) status of these two conformations. To address this problem, we have used the state-dependent TREK-2 inhibitor norfluoxetine that can only bind to the down state, thereby allowing us to distinguish between these two conformations when activated by different stimuli. Our results reconcile these previously contradictory gating models by demonstrating that activation by pressure, temperature, voltage, and pH produce more than one structurally distinct open state and reveal that channel activation does not simply involve switching between the up and down conformations. These results also highlight the diversity of structural mechanisms that K2P channels use to integrate polymodal gating signals.


10.1038/12153 ◽  
1999 ◽  
Vol 2 (9) ◽  
pp. 785-790 ◽  
Author(s):  
Stephanie Schorge ◽  
Seema Gupta ◽  
Zhixin Lin ◽  
Maureen W. McEnery ◽  
Diane Lipscombe

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).


2021 ◽  
Vol 6 (1) ◽  
pp. 2
Author(s):  
Liliana Anchidin-Norocel ◽  
Sonia Amariei ◽  
Gheorghe Gutt

The aim of this paper is the development of a sensor for the quantification of nickel ions in food raw materials and foods. It is believed that about 15% of the human population suffers from nickel allergy. In addition to digestive manifestations, food intolerance to nickel may also have systemic manifestations, such as diffuse dermatitis, diffuse itching, fever, rhinitis, headache, altered general condition. Therefore, it is necessary to control this content of nickel ions for the health of the human population by developing a new method that offers the advantages of a fast, not expensive, in situ, and accurate analysis. For this purpose, bismuth oxide-screen-printed electrodes (SPEs) and graphene-modified SPEs were used with a very small amount of dimethylglyoxime and amino acid L-histidine that were deposited. A potentiostat that displays the response in the form of a cyclic voltammogram was used to study the electrochemical properties of nickel standard solution with different concentrations. The results were compared and the most sensitive sensor proved to be bismuth oxide-SPEs with dimethylglyoxime (Bi2O3/C-dmgH2) with a linear response over a wide range (0.1–10 ppm) of nickel concentrations. Furthermore, the sensor shows excellent selectivity in the presence of common interfering species. The Bi2O3/C-dmgH2 sensor showed good viability for nickel analysis in food samples (cocoa, spinach, cabbage, and red wine) and demonstrated significant advancement in sensor technology for practical applications.


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