scholarly journals In Vivo Neocortical [K]o Modulation by Targeted Stimulation of Astrocytes

2021 ◽  
Vol 22 (16) ◽  
pp. 8658
Author(s):  
Azin EbrahimAmini ◽  
Shanthini Mylvaganam ◽  
Paolo Bazzigaluppi ◽  
Mohamad Khazaei ◽  
Alexander Velumian ◽  
...  

A normally functioning nervous system requires normal extracellular potassium ion concentration ([K]o). Throughout the nervous system, several processes, including those of an astrocytic nature, are involved in [K]o regulation. In this study we investigated the effect of astrocytic photostimulation on [K]o. We hypothesized that in vivo photostimulation of eNpHR-expressing astrocytes leads to a decreased [K]o. Using optogenetic and electrophysiological techniques we showed that stimulation of eNpHR-expressing astrocytes resulted in a significantly decreased resting [K]o and evoked K responses. The amplitude of the concomitant spreading depolarization-like events also decreased. Our results imply that astrocytic membrane potential modification could be a potential tool for adjusting the [K]o.

1972 ◽  
Vol 68 (2_Supplb) ◽  
pp. S217-S236 ◽  
Author(s):  
L. Lambotte ◽  
P. J. Kestens

ABSTRACT Factors responsible for the success of canine liver perfusion are reviewed along with the description of the method used by the authors; emphasis is placed on the avoidance of anoxia, perfusion with blood by the hepatic artery and the portal vein, use of optimal values for haematocrit, pCO2 and temperature. The validity of this method of perfusion is established by biochemical tests but also by its ability to support the viability of livers before transplantation. The monitoring of the perfusion is obtained with an on line digital computer gathering data from autoanalyzers, transducers (temperature, pressure) and from intracellular microelectrodes for the measurement of the membrane potential of the liver cell. Various applications of this system to the study of ionic movements are described. Non-hormonal factors, such as temperature or pH changes modify the ion concentration and the membrane potential; some of the mechanisms involved are briefly discussed. Epinephrine injection produces by stimulation of the α receptor an hepatic potassium loss coupled with an equivalent sodium gain which are concomitant to a marked depolarization. These phenomena can be related to an increase in membrane permeability to the sodium ion. Comparisons are made between the stimulation of a and β adrenergic receptors. The effect of insulin on potassium uptake is studied during liver perfusion and in vivo in order to demonstrate antagonism between insulin on one hand and glucagon and cyclic AMP on the other hand. In conclusion, liver perfusion offers some advantage over in vivo or other in vitro techniques but the method employed must maintain the liver in perfect functional condition. The measurement of membrane potential could be used to evaluate the viability of the perfused liver.


1996 ◽  
Vol 76 (2) ◽  
pp. 1015-1024 ◽  
Author(s):  
I. L. Kopysova ◽  
S. M. Korogod ◽  
J. Durand ◽  
S. Tyc-Dumont

1. In vivo experiments have shown that extracellular microelectrophoretic application of N-methyl-D-aspartate (NMDA) induced oscillatory plateau potentials with bursts of action potentials in rat abducens motoneurons. The period of these slow NMDA oscillations could be altered by single trigeminal non-NMDA excitatory input delivered at low frequency during the NMDA oscillations. 2. A resetting of the oscillations was observed depending on the phase of slow oscillatory cycle during which the trigeminal excitation occurred. 3. We investigated local mechanisms responsible for the phase-dependent modifications of NMDA oscillations, including contributions of voltage and concentration transients, in the mathematical model of the isopotential membrane compartment equipped with voltage-gated Na+, K+, and Ca2+ channels, with Ca2+-dependent K+ channels, and with ligand-gated NMDA and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels. The faithful model was constructed with the use of models described earlier, which were modified by increasing time constants of kinetic variables of all voltage-gated conductances and by including coupled dynamics of voltages and ion concentrations. The changes in ion concentrations were produced near the membrane by transmembrane currents and removal mechanisms (pumps, diffusion). 4. This work focuses on local arrangement of voltage- and ligand-gated conductances and on local ion concentration changes in two separate pools: the postsynaptic pool of AMPA receptors and the extrasynaptic pool. In terms of the electrotonic and diffusional length constants, these pools were electrotonically close but diffusionally remote. 5. It was found that the effect of resetting can be produced by a local interaction between plateau and spike-generating conductances and glutamate receptors. 6. In vivo phase-dependent interactions between NMDA oscillations and AMPA synaptic input were reproduced by the local model only when changes in intracellular sodium and extracellular potassium concentrations were taken into account and the mechanisms of ion removal from postsynaptic pools had slower kinetics than the fast pump system operating in the extracellular pool. 7. Postsynaptic changes in ion concentrations of Na+ and K+ in intra- and extracellular layers near the membrane shift of Nernst equilibrium potentials for these ions depending on the phase of activation of synaptic input. Thus Na+ and k+ components of all transmembrane currents involved in the pattern generation are differently affected by synaptic action during the oscillations. We conclude that slow postsynaptic changes in ion concentrations near the membrane play a key role in the resetting of the NMDA oscillations.


10.1114/1.136 ◽  
1998 ◽  
Vol 26 (6) ◽  
pp. 1010-1021 ◽  
Author(s):  
Bonnie B. Punske ◽  
Wayne E. Cascio ◽  
Connie Engle ◽  
H. Troy Nagle ◽  
Leonard S. Gettes ◽  
...  

2021 ◽  
Author(s):  
Shivangi M Inamdar ◽  
Colten K Lankford ◽  
Deepak Poria ◽  
Joseph G Laird ◽  
Eduardo Solessio ◽  
...  

The voltage-gated potassium channel responsible for controlling photoreceptor signaling is a heteromeric complex of Kv2.1 subunits with a regulatory Kv8.2 subunit. Kv2.1/Kv8.2 channels are localized to the photoreceptor inner segment and carry IKx, largely responsible for setting the photoreceptor resting membrane potential. Mutations in Kv8.2 result in childhood-onset Cone Dystrophy with Supernormal Rod Response (CDSRR). We generated a Kv8.2 knockout (KO) mouse and examined retinal signaling and photoreceptor degeneration to gain deeper insight into the complex phenotypes of this disease. Using electroretinograms we show that there is a tradeoff between delayed or reduced signaling from rods depending on the intensity of the light stimulus, consistent with reduced capacity for light-evoked changes in membrane potential. The delayed response was not seen ex vivo where extracellular potassium levels are the same, so we conclude the in vivo alteration is influenced by ionic imbalance. We observed mild retinal degeneration. Signaling from cones was reduced but there was no loss of cone density. Loss of Kv8.2 altered responses to flickering light with responses attenuated at high frequencies and altered in shape at low frequencies. The Kv8.2 KO line on an all-cone retina background had reduced cone signaling associated with degeneration. We conclude that Kv8.2 is required by rods and cones for responding to dynamic changes in lighting. The timing and cell type affected by degeneration is different in the mouse and human but there is a window of time in both for therapeutic intervention.


1978 ◽  
Vol 176 (2) ◽  
pp. 463-474 ◽  
Author(s):  
David G. Nicholls

The mechanism whereby rat liver mitochondria regulate the extramitochondrial concentration of free Ca2+ was investigated. At 30°C and pH7.0, mitochondria can maintain a steady-state pCa2+0 (the negative logarithm of the free extramitochondrial Ca2+ concentration) of 6.1 (0.8μm). This represents a true steady state, as slight displacements in pCa2+0 away from 6.1 result in net Ca2+ uptake or efflux in order to restore pCa2+0 to its original value. In the absence of added permeant weak acid, the steady-state pCa2+0 is virtually independent of the Ca2+ accumulated in the matrix until 60nmol of Ca2+/mg of protein has been taken up. The steady-state pCa2+0 is also independent of the membrane potential, as long as the latter parameter is above a critical value. When the membrane potential is below this value, pCa2+0 is variable and appears to be governed by thermodynamic equilibration of Ca2+ across a Ca2+ uniport. Permeant weak acids increase, and N-ethylmaleimide decreases, the capacity of mitochondria to buffer pCa2+0 in the region of 6 (1μm-free Ca2+) while accumulating Ca2+. Permeant acids delay the build-up of the transmembrane pH gradient as Ca2+ is accumulated, and consequently delay the fall in membrane potential to values insufficient to maintain a pCa2+0 of 6. The steady-state pCa2+0 is affected by temperature, incubation pH and Mg2+. The activity of the Ca2+ uniport, rather than that of the respiratory chain, is rate-limiting when pCa2+0 is greater than 5.3 (free Ca2+ less than 5μm). When the Ca2+ electrochemical gradient is in excess, the activity of the uniport decreases by 2-fold for every 0.12 increase in pCa2+0 (fall in free Ca2+). At pCa2+0 6.1, the activity of the Ca2+ uniport is kinetically limited to 5nmol of Ca2+/min per mg of protein, even when the Ca2+ electrochemical gradient is large. A steady-state cycling of Ca2+ through independent influx and efflux pathways provides a model which is kinetically and thermodynamically consistent with the present observations, and which predicts an extremely precise regulation of pCa2+0 by liver mitochondria in vivo.


2008 ◽  
Vol 121 (24) ◽  
pp. 2584-2591
Author(s):  
Zhen-tao LIANG ◽  
Xian-pei WANG ◽  
Qiu-tang ZENG ◽  
Yu-hua LIAO ◽  
An-ruo ZOU ◽  
...  

1976 ◽  
Vol 39 (6) ◽  
pp. 1184-1192 ◽  
Author(s):  
W. R. Schlue

1. The sensory neurons in the leech central nervous system differ in their accommodation to linearly rising currents. Advantage was taken of these differences to study the ionic mechanism of accommodation in single pairs of N (noxious), P (pressure), and T (touch) cells. 2. Nonlinearities in membrane-potential changes and current-voltage relationships with square-wave and ramp currents are more pronounced in P and T cells than in N cells. The accommodation coefficients increase in conditions that reflect this delayed rectification. When rectification is absent, the accommodation coefficients depart from unity only slightly or not at all. 3. Accommodation coefficients remain unchanged when half of the chloride in the bathing medium is replaced by sulfate. Accommodation coefficients become greater when the extracellular potassium concentration is reduced from 4 to 0 mM, and decrease when the concentration is raised to 8 mM. The membrane potential changes by only a few millivolts. 4. As extracellular potassium concentration is increased, the action potential is lengthened and the maximal rate of fall of the action potential is reduced. With concentrations greater than 4 mM these relationships are linear, but depart from linearity at lower concentrations. The amplitude of the undershoot decreases linearly as the extracellular potassium concentration increases from 4 to 16 mM, and increases non-linearly at concentrations below 4 mM. 5. The rapid accommodation of leech neurons is based primarily on an increased potassium conductance. The possibility is considered that concentration changes like those produced experimentally may occur naturally, affecting integrative processes in the central nervous system.


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