Current-Voltage Relationship Considering the Direction of the Electrical Field in Mixed Ionic-Electronic Solid Conductors

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Shigetomo Suyama ◽  
Alexandra Ralevski ◽  
Zhong-Wu Liu ◽  
Marcelo O Dietrich ◽  
Toshihiko Yada ◽  
...  

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.


1996 ◽  
Vol 270 (6) ◽  
pp. C1807-C1814 ◽  
Author(s):  
L. Liu ◽  
S. A. Simon

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.


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

1990 ◽  
Vol 151 (1) ◽  
pp. 21-39 ◽  
Author(s):  
JONATHAN A. DAVID ◽  
DAVID B. SATTELLE

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


1991 ◽  
Vol 260 (5) ◽  
pp. C900-C909 ◽  
Author(s):  
D. M. Bers ◽  
L. V. Hryshko ◽  
S. M. Harrison ◽  
D. D. Dawson

Extracellular Ca (Cao) depletions that occur during cardiac muscle contractions are indicative of net Ca entry. Buffering Cao concentration ([Ca]o) with citrate can limit the magnitude of these Cao depletions [e.g., Shattock and Bers. Am. J. Physiol. 256 (Cell Physiol. 25): C813-C822, 1989] which theoretically would allow more Ca entry and consequently greater force at the same free [Ca]o. However, Shimoni and Ginsburg [Am. J. Physiol. 252 (Cell Physiol. 21): C248-C252, 1987] have shown that citrate inhibits cardiac contractions and suggested that this was due to its Ca-buffering action (i.e., dissipating a local elevation of [Ca] at the outer sarcolemmal surface and thereby decreasing Ca influx). To examine the effects of Ca buffering per se, we compared the effects of four low-affinity Ca buffers [citrate, nitrilotriacetic acid (NTA), dipicolinic acid (DPA), and acetamidoiminodiacetic acid (ADA)] on several cardiac preparations. In Mg-free medium with 2 mM free Ca (measured using murexide), citrate, DPA, and ADA (10 mM) decreased the force of twitch contractions in rabbit ventricle to 76 +/- 2, 60 +/- 2, and 85 +/- 2%, respectively, but 10 mM NTA increased force slightly to 105 +/- 2%. No simple correlation was observed between the Ca affinity of the buffer and its effect on tension. These effects were not due to changes in sarcoplasmic reticulum (SR) Ca loading because rapid cooling contractures were not affected and similar results were observed in the presence of caffeine or ryanodine. The depressant effects of citrate and ADA on tension were greater at pH 5.5-6 and ADA had no effect at pH 8.5. Thus the depressant effect is stronger with more protonated forms of citrate and ADA, which are also poorer Ca buffers. Citrate (but not NTA) decreased Ca current in whole cell voltage clamp and shifted the current-voltage relationship and reversal potential to more negative potentials. Citrate decreased Ca current more effectively at higher citrate and lower Ca concentrations. We conclude that citrate (and some other weak Ca buffers) may directly decrease Ca current and contraction in a manner independent of Ca buffering ability.


2020 ◽  
Vol 21 (24) ◽  
pp. 9639
Author(s):  
Yeonju Bae ◽  
Jae Hyouk Choi ◽  
Kanghyun Ryoo ◽  
Ajung Kim ◽  
Osung Kwon ◽  
...  

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.


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