ATP-mediated Increase in H+ Flux from Retinal Müller Cells: a Role for Na+/H+ Exchange

2020 ◽  
Author(s):  
Boriana K Tchernookova ◽  
Michael W Gongwer ◽  
Alexis George ◽  
Brock Goeglein ◽  
Alyssa M Powell ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Neurotransmitter Release ◽  
Müller Cells ◽  
Cell Voltage ◽  
Extracellular Atp ◽  
Extracellular Potassium ◽  
Tiger Salamander ◽  
Synaptic Connections ◽  
Muller Cells ◽  
Extracellular Sodium

Small alterations in extracellular H+ can profoundly alter neurotransmitter release by neurons. We examined mechanisms by which extracellular ATP induces an extracellular H+ flux from Müller glial cells, which surround synaptic connections throughout the vertebrate retina. Müller glia were isolated from tiger salamander retinae and H+ fluxes examined using self-referencing H+-selective microelectrodes. Experiments were performed in 1 mM HEPES with no bicarbonate present. Replacement of extracellular sodium by choline decreased H+ efflux induced by 10 µM ATP by 75%. ATP-induced H+ efflux was also reduced by Na+/H+ exchange inhibitors. Amiloride reduced H+ efflux initiated by 10 µM ATP by 60%, while 10 µM cariporide decreased by 37%, and 25 µM zoniporide reduced H+ flux by 32%. ATP-induced H+ fluxes were not significantly altered by the K+/H+ pump blockers SCH28080 or TAK438, and replacement of all extracellular chloride with gluconate was without effect on H+ fluxes. Recordings of ATP-induced H+ efflux from cells simultaneously whole-cell voltage-clamped revealed no effect of membrane potential from -70 mV to 0 mV. Restoration of extracellular potassium after cells were bathed in 0 mM potassium produced a transient alteration in ATP-dependent H+ efflux. The transient response to extracellular potassium occurred only when extracellular sodium was present and was abolished by 1 mM ouabain, suggesting alterations in sodium gradients mediated by Na+/K ATPase activity. Our data indicate that the majority of H+ efflux elicited by extracellular ATP from isolated Müller cells is mediated by Na+/H+ exchange.

scholarly journals Extracellular H+ fluxes from tiger salamander Müller (glial) cells measured using self-referencing H+-selective microelectrodes

2017 ◽  
Vol 118 (6) ◽  
pp. 3132-3143 ◽  
Author(s):  
Matthew A. Kreitzer ◽  
David Swygart ◽  
Meredith Osborn ◽  
Blair Skinner ◽  
Chad Heer ◽  
...  
Keyword(s):  
Glial Cells ◽  
Müller Cells ◽  
Bicarbonate Transport ◽  
Extracellular Potassium ◽  
Tiger Salamander ◽  
Muller Cells ◽  
Extracellular Acidification ◽  
Müller Glial Cells ◽  
Bicarbonate Transporter ◽  
Induced Changes

Self-referencing H+-selective electrodes were used to measure extracellular H+ fluxes from Müller (glial) cells isolated from the tiger salamander retina. A novel chamber enabled stable recordings using H+-selective microelectrodes in a self-referencing format using bicarbonate-based buffer solutions. A small basal H+ flux was observed from the end foot region of quiescent cells bathed in 24 mM bicarbonate-based solutions, and increasing extracellular potassium induced a dose-dependent increase in H+ flux. Barium at 6 mM also increased H+ flux. Potassium-induced extracellular acidifications were abolished when bicarbonate was replaced by 1 mM HEPES. The carbonic anhydrase antagonist benzolamide potentiated the potassium-induced extracellular acidification, while 300 μM DIDS, 300 μM SITS, and 30 μM S0859 significantly reduced the response. Potassium-induced extracellular acidifications persisted in solutions lacking extracellular calcium, although potassium-induced changes in intracellular calcium monitored with Oregon Green were abolished. Exchange of external sodium with choline also eliminated the potassium-induced extracellular acidification. Removal of extracellular sodium by itself induced a transient alkalinization, and replacement of sodium induced a transient acidification, both of which were blocked by 300 μM DIDS. Recordings at the apical portion of the cell showed smaller potassium-induced extracellular H+ fluxes, and removal of the end foot region further decreased the H+ flux, suggesting that the end foot was the major source of acidifications. These studies demonstrate that self-referencing H+-selective electrodes can be used to monitor H+ fluxes from retinal Müller cells in bicarbonate-based solutions and confirm the presence of a sodium-coupled bicarbonate transporter, the activity of which is largely restricted to the end foot of the cell. NEW & NOTEWORTHY The present study uses self-referencing H+-selective electrodes for the first time to measure H+ fluxes from Müller (glial) cells isolated from tiger salamander retina. These studies demonstrate bicarbonate transport as a potent regulator of extracellular levels of acidity around Müller cells and point toward a need for further studies aimed at addressing how such glial cell pH regulatory mechanisms may shape neuronal signaling.

scholarly journals Extracellular K+ activity changes related to electroretinogram components. II. Rabbit (E-type) retinas.

1985 ◽  
Vol 85 (6) ◽  
pp. 911-931 ◽  
Author(s):  
E Dick ◽  
R F Miller ◽  
S Bloomfield
Keyword(s):  
Retinal Pigment Epithelium ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Müller Cells ◽  
Extracellular Potassium ◽  
Muller Cells ◽  
Positive Component ◽  
Pharmacological Agents ◽  
Slow Piii ◽  
K Activity

Electroretinogram (ERG) and extracellular potassium activity (K+o) measurements were carried out in isolated superfused rabbit eyecup preparations under control conditions and during the application of pharmacological agents that selectively modify the light-responsive retinal network. Light-evoked K+o changes in the rabbit (E-type) retina resemble those previously described in amphibian (I-type) retinas. Different components of the light-evoked K+o changes can be distinguished on the bases of retinal depth, V vs. log I properties, and their responses to pharmacological agents. We find two separable sources of light-evoked increases in extracellular K+: a proximal source and a distal source. The properties of the distal light-evoked K+o increase are consistent with the hypothesis that it initiates a K+-mediated current through Müller cells that is detected as the primary voltage of the electroretinographic b-wave. These experiments also support previous studies indicating that both the corneal-positive component of c-wave and the corneal-negative slow PIII potential result from K+-mediated influences on, respectively, the retinal pigment epithelium and Müller cells.

scholarly journals The membrane potential of human platelets

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 180-185
Author(s):  
LT Friedhoff ◽  
M Sonenberg
Keyword(s):  
Membrane Potential ◽  
Calcium Ion ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Ion Concentration ◽  
Extracellular Potassium ◽  
Ion Concentrations ◽  
Calcium Ion Concentration ◽  
Extracellular Sodium

The membrane potential of the human platelet was investigated using the membrane potential probes 3,3′-dipropyl-2,2′-thiadicarbocyanine iodide and tritiated triphenylmethylphosphonium bromide. The membrane potential in physiologic buffer was estimated to be 52–60 mV inside negative. The membrane was depolarized when extracellular potassium or hydrogen ion concentrations were increased. Changes in extracellular sodium, chloride, or calcium ion concentration had no measurable effect on membrane potential. Elevated extracellular potassium has been shown to increase platelet sensitivity to the aggregating agent, adenosine diphosphate. Our results show that changes in extracellular ion concentrations that depolarize platelets increase platelet sensitivity to aggregating agents. These results suggest that membrane potential changes may play a role in modulating the response of platelets to aggregating agents.

scholarly journals The membrane potential of human platelets

Blood ◽  
1983 ◽  
Vol 61 (1) ◽  
pp. 180-185 ◽  
Author(s):  
LT Friedhoff ◽  
M Sonenberg
Keyword(s):  
Membrane Potential ◽  
Calcium Ion ◽  
Human Platelet ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Ion Concentration ◽  
Extracellular Potassium ◽  
Ion Concentrations ◽  
Calcium Ion Concentration ◽  
Extracellular Sodium

Abstract The membrane potential of the human platelet was investigated using the membrane potential probes 3,3′-dipropyl-2,2′-thiadicarbocyanine iodide and tritiated triphenylmethylphosphonium bromide. The membrane potential in physiologic buffer was estimated to be 52–60 mV inside negative. The membrane was depolarized when extracellular potassium or hydrogen ion concentrations were increased. Changes in extracellular sodium, chloride, or calcium ion concentration had no measurable effect on membrane potential. Elevated extracellular potassium has been shown to increase platelet sensitivity to the aggregating agent, adenosine diphosphate. Our results show that changes in extracellular ion concentrations that depolarize platelets increase platelet sensitivity to aggregating agents. These results suggest that membrane potential changes may play a role in modulating the response of platelets to aggregating agents.

scholarly journals Review and Hypothesis: A Potential Common Link Between Glial Cells, Calcium Changes, Modulation of Synaptic Transmission, Spreading Depression, Migraine, and Epilepsy—H+

2021 ◽  
Vol 15 ◽  
Author(s):  
Robert Paul Malchow ◽  
Boriana K. Tchernookova ◽  
Ji-in Vivien Choi ◽  
Peter J. S. Smith ◽  
Richard H. Kramer ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Intracellular Calcium ◽  
Glial Cells ◽  
Spreading Depression ◽  
Müller Cells ◽  
Extracellular Atp ◽  
Muller Cells ◽  
Radial Glial Cells ◽  
Synaptic Modulation ◽  
Radial Glial

There is significant evidence to support the notion that glial cells can modulate the strength of synaptic connections between nerve cells, and it has further been suggested that alterations in intracellular calcium are likely to play a key role in this process. However, the molecular mechanism(s) by which glial cells modulate neuronal signaling remains contentiously debated. Recent experiments have suggested that alterations in extracellular H+ efflux initiated by extracellular ATP may play a key role in the modulation of synaptic strength by radial glial cells in the retina and astrocytes throughout the brain. ATP-elicited alterations in H+ flux from radial glial cells were first detected from Müller cells enzymatically dissociated from the retina of tiger salamander using self-referencing H+-selective microelectrodes. The ATP-elicited alteration in H+ efflux was further found to be highly evolutionarily conserved, extending to Müller cells isolated from species as diverse as lamprey, skate, rat, mouse, monkey and human. More recently, self-referencing H+-selective electrodes have been used to detect ATP-elicited alterations in H+ efflux around individual mammalian astrocytes from the cortex and hippocampus. Tied to increases in intracellular calcium, these ATP-induced extracellular acidifications are well-positioned to be key mediators of synaptic modulation. In this article, we examine the evidence supporting H+ as a key modulator of neurotransmission, review data showing that extracellular ATP elicits an increase in H+ efflux from glial cells, and describe the potential signal transduction pathways involved in glial cell—mediated H+ efflux. We then examine the potential role that extracellular H+ released by glia might play in regulating synaptic transmission within the vertebrate retina, and then expand the focus to discuss potential roles in spreading depression, migraine, epilepsy, and alterations in brain rhythms, and suggest that alterations in extracellular H+ may be a unifying feature linking these disparate phenomena.

Modulation of horizontal cell function by GABAA and GABAC receptors in dark- and light-adapted tiger salamander retina

1999 ◽  
Vol 16 (5) ◽  
pp. 967-979 ◽  
Author(s):  
XIONG-LI YANG ◽  
FAN GAO ◽  
SAMUEL M. WU
Keyword(s):  
Membrane Potential ◽  
Gaba Receptors ◽  
Cell Function ◽  
Horizontal Cell ◽  
Reversal Potential ◽  
Cell Voltage ◽  
Chloride Conductance ◽  
Tiger Salamander ◽  
Light Responses ◽  
Gaba Transporters

The physiological function of GABA transporters and GABA receptors in retinal horizontal cells (HCs) under dark- and light-adapted conditions were studied by whole-cell voltage clamp and intracellular recording techniques in retinal slices and whole-mounted isolated retinas of the larval tiger salamander. Puff application of GABA in picrotoxin elicited a NO-711 (a potent GABA transporter blocker)-sensitive inward current that did not exhibit a reversal potential in the physiological range, consistent with the idea that these HCs contain electrogenic GABA transporters. Application of GABA in NO-711 elicited a chloride current in HCs; about half of the current was suppressed by bicuculline or I4AA (a GABAC receptor antagonist), and the remaining half was suppressed by bicuculline + I4AA or picrotoxin. In whole-mount retinas, NO-711, bicuculline, I4AA, or picrotoxin hyperpolarized the HCs and enhanced the light responses under dark-adapted conditions, and blocked the time-dependent recovery of HC membrane potential and light responses during background illumination. Based on the parallel conductance model, GABA released in darkness mediates a chloride conductance about three times greater than the leak conductance or the glutamate-gated cation conductance. About half of this chloride conductance is mediated by GABAA receptors, and the other half is mediated by GABAC receptors. These results suggest that GABA released from HCs through the NO-711-sensitive GABA transporters activates GABAA and GABAC receptors, resulting in chloride conductance increase which leads to a HC depolarization and reduction of the light response. Additionally, GABA transporters also mediate GABA release in background light that is responsible for the recovery of HC membrane potential and light responses.

Relationship between Muller cell responses, a local transretinal potential, and potassium flux

1977 ◽  
Vol 40 (2) ◽  
pp. 244-259 ◽  
Author(s):  
C. J. Karowski ◽  
L. M. Proenza
Keyword(s):  
Müller Cells ◽  
Müller Cell ◽  
Extracellular Potassium ◽  
Muller Cells ◽  
Light Onset ◽  
M Wave ◽  
Cell Responses ◽  
Stimulus Parameters ◽  
Muller Cell ◽  
Cell Depolarization

1. In the Necturus retina, light-evoked field potentials, Muller (glial) cell responses, and extracellular potassium ion concentration ([K+]0) were recorded and found to exhibit the three-way correlation characteristic of these variables elsewhere in the nervous system. 2. Muller cell responses to a flashed spot or annulus consist primarily of slow depolarizations at both light onset and offset. The responses are maximum to 0.5-mm-diameter spots and decrease with larger diameters. Responses to stimulus intensity and flicker were also used to characterize Muller cell behavior. 3. In response to long-duration stimuli, the initial Muller cell depolarization is followed by a very slow hyperpolarization, which is likely the origin of slow PIII. 4. A new extracellular potential is described, the M-wave, the basic properties of which suggest that it is generated by Muller cells. Moreover, the M-wave and Muller cells show remarkably similar behavior to a wide variety of stimulus parameters. 5. In the proximal retina, [K+]0 increases at both light onset and offset with a time course similar to that of Muller cell depolarizing responses. This K+ increase also behaves similarly to the Muller cell depolarization in response to changes in stimulus parameters. 6. It is concluded that light stimulation leads to an increase in [K+]0 in the proximal retina and that this increase depolarizes Muller cells whose associated currents, in turn, generate the M-wave.

Calcium-activated chloride channels in müller cells acutely isolated from tiger salamander retina

Glia ◽  
2005 ◽  
Vol 53 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Nicole C. Welch ◽  
Melanie R. Lalonde ◽  
Steven Barnes ◽  
Melanie E.M. Kelly
Keyword(s):  
Chloride Channels ◽  
Müller Cells ◽  
Tiger Salamander ◽  
Muller Cells

Developmental Regulation of Calcium Channel-Mediated Currents in Retinal Glial (Müller) Cells

2000 ◽  
Vol 84 (6) ◽  
pp. 2975-2983 ◽  
Author(s):  
A. Bringmann ◽  
S. Schopf ◽  
A. Reichenbach
Keyword(s):  
Glial Cells ◽  
Low Voltage ◽  
Developmental Regulation ◽  
Müller Cells ◽  
Cell Voltage ◽  
Charge Carriers ◽  
Muller Cells ◽  
Isolated Cells ◽  
Radial Glial Cells ◽  
Radial Glial

Whole cell voltage-clamp recordings of freshly isolated cells were used to study changes in the currents through voltage-gated Ca2+ channels during the postnatal development of immature radial glial cells into Müller cells of the rabbit retina. Using Ba2+ or Ca2+ ions as charge carriers, currents through transient low-voltage-activated (LVA) Ca2+ channels were recorded in cells from early postnatal stages, with an activation threshold at −60 mV and a peak current at −25 mV. To increase the amplitude of currents through Ca2+ channels, Na+ ions were used as the main charge carriers, and currents were recorded in divalent cation-free bath solutions. Currents through transient LVA Ca2+ channels were found in all radial glial cells from retinae between postnatal days 2 and 37. The currents activated at potentials positive to −80 mV and displayed a maximum at −40 mV. The amplitude of LVA currents increased during the first postnatal week; after postnatal day 6, the amplitude remained virtually constant. The density of LVA currents was highest at early postnatal days (days 2–5: 13 pA/pF) and decreased to a stable, moderate level within the first three postnatal weeks (3 pA/pF). A significant expression of currents through sustained, high-voltage-activated Ca2+ channels was found after the third postnatal week in ∼25% of the investigated cells. The early and sole expression of transient currents at high-density may suggest that LVA Ca2+ channels are involved in early developmental processes of rabbit Müller cells.

scholarly journals Activation of retinal glial (Müller) cells by extracellular ATP induces pronounced increases in extracellular H+ flux

PLoS ONE ◽  
2018 ◽  
Vol 13 (2) ◽  
pp. e0190893 ◽  
Author(s):  
Boriana K. Tchernookova ◽  
Chad Heer ◽  
Marin Young ◽  
David Swygart ◽  
Ryan Kaufman ◽  
...  
Keyword(s):  
Müller Cells ◽  
Extracellular Atp ◽  
Muller Cells
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