The ATP-Releasing Maxi-Cl Channel: Its Identity, Molecular Partners, and Physiological/Pathophysiological Implications

The Maxi-Cl phenotype accounts for the majority (app. 60%) of reports on the large-conductance maxi-anion channels (MACs) and has been detected in almost every type of cell, including placenta, endothelium, lymphocyte, cardiac myocyte, neuron, and glial cells, and in cells originating from humans to frogs. A unitary conductance of 300–400 pS, linear current-to-voltage relationship, relatively high anion-to-cation selectivity, bell-shaped voltage dependency, and sensitivity to extracellular gadolinium are biophysical and pharmacological hallmarks of the Maxi-Cl channel. Its identification as a complex with SLCO2A1 as a core pore-forming component and two auxiliary regulatory proteins, annexin A2 and S100A10 (p11), explains the activation mechanism as Tyr23 dephosphorylation at ANXA2 in parallel with calcium binding at S100A10. In the resting state, SLCO2A1 functions as a prostaglandin transporter whereas upon activation it turns to an anion channel. As an efficient pathway for chloride, Maxi-Cl is implicated in a number of physiologically and pathophysiologically important processes, such as cell volume regulation, fluid secretion, apoptosis, and charge transfer. Maxi-Cl is permeable for ATP and other small signaling molecules serving as an electrogenic pathway in cell-to-cell signal transduction. Mutations at the SLCO2A1 gene cause inherited bone and gut pathologies and malignancies, signifying the Maxi-Cl channel as a perspective pharmacological target.

Spadin Modulates Astrocytic Passive Conductance via Inhibition of TWIK-1/TREK-1 Heterodimeric Channels

Astrocytes, the most abundant cell type in the brain, are non-excitable cells and play critical roles in brain function. Mature astrocytes typically exhibit a linear current–voltage relationship termed passive conductance, which is believed to enable astrocytes to maintain potassium homeostasis in the brain. We previously demonstrated that TWIK-1/TREK-1 heterodimeric channels mainly contribute to astrocytic passive conductance. However, the molecular identity of astrocytic passive conductance is still controversial and needs to be elucidated. Here, we report that spadin, an inhibitor of TREK-1, can dramatically reduce astrocytic passive conductance in brain slices. A series of gene silencing experiments demonstrated that spadin-sensitive currents are mediated by TWIK-1/TREK-1 heterodimeric channels in cultured astrocytes and hippocampal astrocytes from brain slices. Our study clearly showed that TWIK-1/TREK-1-heterodimeric channels can act as the main molecular machinery of astrocytic passive conductance, and suggested that spadin can be used as a specific inhibitor to control astrocytic passive conductance.

Effects of energy band structure on gallium arsenide based MOSFET

This research work is focused on material science and semiconductor engineering. It emphasized on the semiconductor material such as Gallium arsenide (GaAs). The Gallium arsenide semiconductor material was used as a group III-V compound for metal-oxide semiconductor field effect transistor (MOSFET) modeling. The band-gap energy structures were analyzed by using material parameters such as Varshni parameters, temperature and doping concentrations. Then, an electrical characteristic was carried out depending on the current and voltage relationship. The current flowing in the device is associated with a gate voltage applied to the device. From this paper, the analysis of MOSFET modeling was investigated using mathematical equations and MATLAB simulation.

A Type of Hysteretic Nonlinear Model of Piezoelectric Sensor

In this paper, a type of hysteretic constitutive model of piezoelectric sensor was proposed. Nonlinear differential terms were developed to express the hysteresis phenomena of displacement-voltage relationship of piezoelectric ceramics. Based on the model, the dynamic model of a PZT sensor was established. The nonlinear dynamic behaviours of a PZT sensor were analyzed, and the relationship between the outside excitation and the voltage of a PZT sensor was obtained. Theoretical results show that there are many kinds of frequencies in the output voltage, which are caused by the PZT’s hysteresis characteristics.

One drug-sensitive subunit is sufficient for a near-maximal retigabine effect in KCNQ channels

Retigabine is an antiepileptic drug and the first voltage-gated potassium (Kv) channel opener to be approved for human therapeutic use. Retigabine is thought to interact with a conserved Trp side chain in the pore of KCNQ2–5 (Kv7.2–7.5) channels, causing a pronounced hyperpolarizing shift in the voltage dependence of activation. In this study, we investigate the functional stoichiometry of retigabine actions by manipulating the number of retigabine-sensitive subunits in concatenated KCNQ3 channel tetramers. We demonstrate that intermediate retigabine concentrations cause channels to exhibit biphasic conductance–voltage relationships rather than progressive concentration-dependent shifts. This suggests that retigabine can exert its effects in a nearly “all-or-none” manner, such that channels exhibit either fully shifted or unshifted behavior. Supporting this notion, concatenated channels containing only a single retigabine-sensitive subunit exhibit a nearly maximal retigabine effect. Also, rapid solution exchange experiments reveal delayed kinetics during channel closure, as retigabine dissociates from channels with multiple drug-sensitive subunits. Collectively, these data suggest that a single retigabine-sensitive subunit can generate a large shift of the KCNQ3 conductance–voltage relationship. In a companion study (Wang et al. 2018. J. Gen. Physiol. https://doi.org/10.1085/jgp.201812014), we contrast these findings with the stoichiometry of a voltage sensor-targeted KCNQ channel opener (ICA-069673), which requires four drug-sensitive subunits for maximal effect.

Four drug-sensitive subunits are required for maximal effect of a voltage sensor–targeted KCNQ opener

KCNQ2-5 (Kv7.2–Kv7.5) channels are strongly influenced by an emerging class of small-molecule channel activators. Retigabine is the prototypical KCNQ activator that is thought to bind within the pore. It requires the presence of a Trp side chain that is conserved among retigabine-sensitive channels but absent in the retigabine-insensitive KCNQ1 subtype. Recent work has demonstrated that certain KCNQ openers are insensitive to mutations of this conserved Trp, and that their effects are instead abolished or attenuated by mutations in the voltage-sensing domain (VSD). In this study, we investigate the stoichiometry of a VSD-targeted KCNQ2 channel activator, ICA-069673, by forming concatenated channel constructs with varying numbers of drug-insensitive subunits. In homomeric WT KCNQ2 channels, ICA-069673 strongly stabilizes an activated channel conformation, which is reflected in the pronounced deceleration of deactivation and leftward shift of the conductance–voltage relationship. A full complement of four drug-sensitive subunits is required for maximal sensitivity to ICA-069673—even a single drug-insensitive subunit leads to significantly weakened effects. In a companion article (see Yau et al. in this issue), we demonstrate very different stoichiometry for the action of retigabine on KCNQ3, for which a single retigabine-sensitive subunit enables near-maximal effect. Together, these studies highlight fundamental differences in the site and mechanism of activation between retigabine and voltage sensor–targeted KCNQ openers.

Comparison between Carbon Nanotube-Based, Graphite-Based, and Rice Hull Carbon-Based Electrodes with Rice Hull Silica as Catalyst for Electrochemical Detection of Copper

This study aimed to determine the copper ion-sensing ability of a carbon nanotube (CNT)-based sensor with carbonized rice hull (CRH) as catalyst. The 50:50 CNT-CRH electrode was compared to 100% graphite, 100% CRH, 100% CNT, 50:50 graphite-CRH, and 70:30 graphite-CRH electrodes. Copper chloride (CuCl2) concentrations of 0.01M, 0.02M, 0.03M, 0.04M, 0.04M, 0.05M, 0.06, 0.07M, 0.08M, 0.09M, and 0.1M were used to test the response of the electrodes. Five trials were done for each concentration. The 50:50 CNT-CRH electrode exhibited good sensor characteristics such as high sensitivity, low resolution, and high correlation in concentration-voltage relationship. Electrical characterization using three-electrode system showed a linear relationship between the concentrations and voltage response. The 50:50 CNT-CRH electrode exhibited a sensitivity of 0.0619 V/0.01M or 9.7 mV/100ppm and a resolution of 10 ppm/1mV. The electrode also exhibited a high correlation R2 value of 0.933.