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

2020 ◽  
Vol 21 (24) ◽  
pp. 9639
Author(s):  
Yeonju Bae ◽  
Jae Hyouk Choi ◽  
Kanghyun Ryoo ◽  
Ajung Kim ◽  
Osung Kwon ◽  
...  
Keyword(s):  
Brain Slices ◽  
Specific Inhibitor ◽  
Excitable Cells ◽  
Cultured Astrocytes ◽  
Current Voltage ◽  
Molecular Machinery ◽  
Hippocampal Astrocytes ◽  
Current Voltage Relationship ◽  
The Brain ◽  
Voltage Relationship

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.

Somatostatin Increases a Voltage-Insensitive K+ Conductance in Rat CA1 Hippocampal Neurons

1998 ◽  
Vol 79 (3) ◽  
pp. 1230-1238 ◽  
Author(s):  
Paul Schweitzer ◽  
Samuel G. Madamba ◽  
George R. Siggins
Keyword(s):  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Specific Inhibitor ◽  
Outward Current ◽  
Resting Potential ◽  
Resting Membrane Potential ◽  
High Concentration ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Schweitzer, Paul, Samuel G. Madamba, and George R. Siggins. Somatostatin increases a voltage-insensitive K+ conductance in rat CA1 hippocampal neurons. J. Neurophysiol. 79: 1230–1238, 1998. Somatostatin (SST) is a neuropeptide involved in several central processes. In hippocampus, SST hyperpolarizes CA1 pyramidal neurons and augments the K+ M current ( I M). However, the limited involvement of I M at resting potential in these cells suggests that the peptide also may modulate another channel to hyperpolarize hippocampal pyramidal neurons (HPNs). We studied the effect of SST on noninactivating conductances of rat CA1 HPNs in a slice preparation. Using MK886, a specific inhibitor of the enzymatic pathway that leads to the augmentation of I M by SST, we have uncovered and characterized a second conductance activated by the peptide. SST did not affect I M when applied with MK886 or the amplitudes of the slow Ca2+-dependent K+ afterhyperpolarization-current and the cationic Q current but still caused an outward current, indicating that SST acts upon another conductance. In the presence of MK886, SST elicited an outward current that reversed around −100 mV and that displayed a linear current-voltage relationship. Reversal potentials obtained in different external K+ concentrations are consistent with a conductance carried solely by K+ ions. The slope of the current-voltage relationship increased proportionately with the extracellular K+ concentration and remained linear. This suggests that SST opens a voltage-insensitive leak current ( I K(L)) in HPNs not an inwardly rectifying K+ current as reported in other neuron types. A low concentration of extracellular Ba2+ (150 μM) only slightly decreased the SST-induced effect in a voltage-independent manner, whereas a high concentration of Ba2+ (2 mM) completely blocked it. Extracellular Cs+ (2 mM) did not affect the outward SST current but inhibited the inward component. We conclude that SST inhibits HPNs by activating two different K+ conductances: the voltage-insensitive I K(L) and the voltage-dependent I M. The hyperpolarizing effect of SST at resting membrane potential appears to be mainly carried by I K(L), whereas I M dominates at slightly depolarized potentials.

scholarly journals A Na+- and Cl−-activated K+ Channel in the Thick Ascending Limb of Mouse Kidney

2006 ◽  
Vol 127 (2) ◽  
pp. 205-215 ◽  
Author(s):  
Marc Paulais ◽  
Sahran Lachheb ◽  
Jacques Teulon
Keyword(s):  
Basolateral Membrane ◽  
Inward Rectification ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Excitable Cells ◽  
Current Voltage ◽  
Hill Coefficients ◽  
Current Voltage Relationship ◽  
Voltage Relationship ◽  
High Conductance

This study investigates the presence and properties of Na+-activated K+ (KNa) channels in epithelial renal cells. Using real-time PCR on mouse microdissected nephron segments, we show that Slo2.2 mRNA, which encodes for the KNa channels of excitable cells, is expressed in the medullary and cortical thick ascending limbs of Henle's loop, but not in the other parts of the nephron. Patch-clamp analysis revealed the presence of a high conductance K+ channel in the basolateral membrane of both the medullary and cortical thick ascending limbs. This channel was highly K+ selective (PK/PNa ∼ 20), its conductance ranged from 140 to 180 pS with subconductance levels, and its current/voltage relationship displayed intermediate, Na+-dependent, inward rectification. Internal Na+ and Cl− activated the channel with 50% effective concentrations (EC50) and Hill coefficients (nH) of 30 ± 1 mM and 3.9 ± 0.5 for internal Na+, and 35 ± 10 mM and 1.3 ± 0.25 for internal Cl−. Channel activity was unaltered by internal ATP (2 mM) and by internal pH, but clearly decreased when internal free Ca2+ concentration increased. This is the first demonstration of the presence in the epithelial cell membrane of a functional, Na+-activated, large-conductance K+ channel that closely resembles native KNa channels of excitable cells. This Slo2.2 type, Na+- and Cl−-activated K+ channel is primarily located in the thick ascending limb, a major renal site of transcellular NaCl reabsorption.

scholarly journals Plasticity of calcium-permeable AMPA glutamate receptors in Pro-opiomelanocortin neurons

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Shigetomo Suyama ◽  
Alexandra Ralevski ◽  
Zhong-Wu Liu ◽  
Marcelo O Dietrich ◽  
Toshihiko Yada ◽  
...  
Keyword(s):  
Food Deprivation ◽  
High Fat Diet ◽  
Receptor Complex ◽  
High Fat ◽  
Fasted State ◽  
Linear Current ◽  
Current Voltage ◽  
Relationship Of ◽  
Current Voltage Relationship ◽  
Voltage Relationship

POMC neurons integrate metabolic signals from the periphery. Here, we show in mice that food deprivation induces a linear current-voltage relationship of AMPAR-mediated excitatory postsynaptic currents (EPSCs) in POMC neurons. Inhibition of EPSCs by IEM-1460, an antagonist of calcium-permeable (Cp) AMPARs, diminished EPSC amplitude in the fed but not in the fasted state, suggesting entry of GluR2 subunits into the AMPA receptor complex during food deprivation. Accordingly, removal of extracellular calcium from ACSF decreased the amplitude of mEPSCs in the fed but not the fasted state. Ten days of high-fat diet exposure, which was accompanied by elevated leptin levels and increased POMC neuronal activity, resulted in increased expression of Cp-AMPARs on POMC neurons. Altogether, our results show that entry of calcium via Cp-AMPARs is inherent to activation of POMC neurons, which may underlie a vulnerability of these neurons to calcium overload while activated in a sustained manner during over-nutrition.

Capsaicin and nicotine both activate a subset of rat trigeminal ganglion neurons

1996 ◽  
Vol 270 (6) ◽  
pp. C1807-C1814 ◽  
Author(s):  
L. Liu ◽  
S. A. Simon
Keyword(s):  
Trigeminal Ganglion ◽  
Acetylcholine Receptors ◽  
Ganglion Cells ◽  
Whole Cell Patch Clamp ◽  
Current Voltage ◽  
Trigeminal Ganglion Neurons ◽  
Ganglion Neurons ◽  
Relationship Of ◽  
Current Voltage Relationship ◽  
Voltage Relationship

Nicotine and capsaicin produce many similar physiological responses that include pain, irritation, and vasodilation. To determine whether neuronal nicotine acetylcholine receptors (nAChR) are present on capsaicin-sensitive neurons, whole cell patch-clamp recordings were performed on rat trigeminal ganglion cells. It was found that approximately 20% of the total number of neurons tested was activated by both 100 microM nicotine and 1 nM capsaicin. Other subsets of neurons were activated by only one of these compounds, whereas a fourth subset was not activated by either compound. At -60 mV, the magnitude of the capsaicin-activated currents was about three times larger than the magnitude of the nicotine-activated currents. The current-voltage relationship of the nAChR exhibited marked rectification, such that for voltages > or = 0 mV the current was essentially zero. In contrast, the current-voltage relationship of the capsaicin-activated current was ohmic from +/- 60 mV. These data indicate the existence of subsets of capsaicin-sensitive afferent neurons.

Simulation of Na/K Pump Current-Voltage Relationship

1992 ◽  
Vol 671 (1 Ion-Motive AT) ◽  
pp. 449-451 ◽  
Author(s):  
X.-Y. LIU ◽  
T. A. KINARD ◽  
J. R. STIMERS
Keyword(s):  
Pump Current ◽  
Current Voltage ◽  
Current Voltage Relationship ◽  
Voltage Relationship

scholarly journals Ionic Basis of Membrane Potential and of Acetylcholine-evduced Currents in the Cell Body of the Cockroach Fast Coxal Depressor Motor Neurone

1990 ◽  
Vol 151 (1) ◽  
pp. 21-39 ◽  
Author(s):  
JONATHAN A. DAVID ◽  
DAVID B. SATTELLE
Keyword(s):  
Cell Body ◽  
Outward Current ◽  
Motor Neurone ◽  
Resting Potential ◽  
Inward Current ◽  
Current Voltage ◽  
Low K ◽  
Current Voltage Relationship ◽  
Ionic Basis ◽  
Voltage Relationship

The ionic basis of the resting potential and of the response to acetylcholine (ACh) has been investigated in the cell body membrane of the fast coxal depressor motor neurone in the metathoracic ganglion of the cockroach Periplaneta americana. By means of ion-sensitive microelectrodes, intracellular concentrations of three ion species were estimated (mmoll−1): [K+]i, 1443; [Na+]i, 9±1; [Cl−], 7±1. The resting potential of continuously superfused cells was −75.6±1.9mV at 22° C. A change in resting potential of 42.0±2.5mV accompanied a decade change in [K+]o. Experiments with (10−4moll−1) ouabain, Na+ injection, low temperature (10°C) and non-superfused cells indicated the presence of an electrogenic sodium pump. Under current-clamp, the cell body membrane was depolarized by sequentially applied, ionophoretic pulses (500ms duration) of ACh. Under voltage-clamp, such doses of ACh resulted in an inward current which was abolished in low-Na+ saline. Ion-sensitive electrodes revealed an increase in [Na+]i but no change in [Cl−1]j in response to externally applied ACh. The ACh-induced current-voltage relationship was shifted in a negative direction by low-K+ saline. The AChinduced inward current was usually followed by a delayed outward current which reversed at Ek. Low-K+ saline had the same effect on this outward component as depolarizing the membrane. This suggests that the outward current component is carried by K+. The ACh-induced inward current and the delayed outward current were potentiated either when [Ca2+]i was lowered by injecting the calcium chelator BAPTA or by exposure of the cell to low-Ca2+ saline. High-Ca2+ saline reduced the inward component of the response and produced a negative shift in the AChinduced current-voltage relationship. The amplitude of the delayed outward

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