Interstitial volume changes during spreading depression (SD) and SD-like hypoxic depolarization in hippocampal tissue slices

1994 ◽  
Vol 71 (6) ◽  
pp. 2548-2551 ◽  
Author(s):  
J. Jing ◽  
P. G. Aitken ◽  
G. G. Somjen
Keyword(s):  
Spreading Depression ◽  
Volume Changes ◽  
Tissue Slices ◽  
Ion Concentrations ◽  
Ca1 Region ◽  
Interstitial Volume ◽  
High K ◽  
Concentration Changes ◽  
Short Time ◽  
Total Tissue

1. Relative interstitial volume (ISV) was estimated from the concentration changes of iontophoretically administered tetramethyl- and tetraethylammonium (TMA+ and TEA+). Spreading depression (SD) was provoked by high K+, and hypoxic SD-like depolarization (HSD) was induced by withdrawing oxygen. 2. Probe ion concentrations increased dramatically and about equally during SD and HSD, except that in a few hypoxic trials signals became transiently smaller than control. Interstitial volume appeared to decrease on the average by approximately 70%. 3. The ISV that remains patent in CA1 region at the height of SD is < 4% of total tissue volume. Probe ions may occasionally have passed through cell membranes for a short time during hypoxic SD.

Mechanisms of spreading depression: a review of recent findings and a hypothesis

1992 ◽  
Vol 70 (S1) ◽  
pp. S248-S254 ◽  
Author(s):  
G. G. Somjen ◽  
P. G. Aitken ◽  
G. L. Czéh ◽  
O. Herrearas ◽  
J. Jing ◽  
...  
Keyword(s):  
Spreading Depression ◽  
Membrane Resistance ◽  
Extracellular Potassium ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Sequence Of Events ◽  
High K ◽  
Hippocampal Ca1 ◽  
Severe Reduction ◽  
Chemical Stimuli

Spreading depression of Leão (SD) can be provoked by numerous nonspecific mechanical, electrical, and chemical stimuli. A similar, if not identical, phenomenon can be provoked by hypoxia. SD is characterized by drastic depolarization of neurons, severe reduction of membrane resistance, and redistribution of ions across cell membranes. Glial cells also depolarize but retain membrane resistance. Tetraethylammonium hastens the onset of hypoxic SD but reduces the sustained potential shift and K+ outflow from cells; 4-aminopyridine also accelerates SD but has no effect on the voltage shift. N-Methyl-D-aspartate receptor antagonists delay the onset of SD, while nickel and cobalt reduce the amplitude of SD-related redistribution of Ca2+. Yet, no specific blocker of SD has been found. Microdialysis of high-K+ solution in hippocampal CA1 region induces recurrent waves of SD propagating semi-independently in adjacent tissue layers, and a prolonged unstable depressed state that has not previously been described. Neither the release of K+ ions nor of glutamate is the unique agent of SD propagation. On the basis of recent findings we propose a hypothetical sequence of events that reconcile many of the previously seemingly paradoxical observations.Key words: spreading depression, membrane resistance, membrane ion currents, extracellular potassium, extracellular calcium.

Swelling and potassium uptake in cultured astrocytes

1987 ◽  
Vol 65 (5) ◽  
pp. 1051-1057 ◽  
Author(s):  
Wolfgang Walz
Keyword(s):  
Energy Source ◽  
Driving Force ◽  
Primary Cultures ◽  
Volume Changes ◽  
Cultured Astrocytes ◽  
High K ◽  
Ion Activity ◽  
Net Uptake ◽  
Two Phases ◽  
External K

The intracellular water content of astrocytes in primary cultures shows a biphasic swelling pattern on exposure to various increased external K+ concentrations over the range of 1.5–100 mM. The two phases (physiological, 1.5–12 mM K+; pathological, 25–100 mM K+) are based on two different mechanisms. Both can be blocked by low Cl− solutions and involve intensive net uptake of K+. However, the physiological phase consists of the activation of a KCl + NaCl carrier, while the Na+ in turn is pumped out by Na+–K+ ATPase, with a resultant net accumulation of KCl. At pathological K+ concentrations the KCl + NaCl carrier is less active because the Na+ driving force, its energy source, is reduced (owing to depolarization by K+). However, the Donnan equilibrium across the cell membrane is heavily disturbed, which leads to passive KCl accumulation. The results suggest that volume changes in cultured glial cells during exposure to high K+ should be taken into consideration since they disguise K+ accumulation when only ion activity is measured.

Changes in vascular and extravascular volumes of eel muscle in response to catecholamines: the function of the caudal lymphatic heart

1982 ◽  
Vol 96 (1) ◽  
pp. 195-208
Author(s):  
P. S. Davie
Keyword(s):  
Vascular System ◽  
Volume Changes ◽  
Heart Frequency ◽  
Vascular Volume ◽  
Interstitial Volume ◽  
Resistance Vessels ◽  
Lymph Heart ◽  
Capillary Resistance ◽  
High Concentrations ◽  
Lymphatic Heart

1. Vascular volume changes in an isolated saline-perfused eel tail preparation in response to catecholamines were small (less than 2%) and are explicable in terms of changes in volume of pre-capillary resistance vessels. 2. Extravascular-extracellular (interstitial) volume increased less than 3% during infusion of adrenaline (AD) at concentrations of 1 × 10(−6) to 1 × 10(−3) M. Injection of doses of AD and noradrenaline (NA) between 1 nmol and 100 nmol caused maximum interstitial volume changes of less than 11%. 3. Isoprenaline caused only very small changes in vascular and interstitial volume. 4. Caudal lymph heart frequency increases when high concentrations (greater than 1 × 10(−6) M) and doses (greater than 1 nmol) of AD and NA were administered. 5. Caudal lymph heart frequency increases were significantly correlated with changes in outflow after vascular volume adjustments. One function of the caudal lymph heart is to return interstitial fluid to the vascular system.

Heptanol But Not Fluoroacetate Prevents the Propagation of Spreading Depression in Rat Hippocampal Slices

1997 ◽  
Vol 77 (1) ◽  
pp. 9-16 ◽  
Author(s):  
Carlota Largo ◽  
Geoffrey C. Tombaugh ◽  
Peter G. Aitken ◽  
Oscar Herreras ◽  
George G. Somjen
Keyword(s):  
Synaptic Transmission ◽  
Gap Junctions ◽  
Spreading Depression ◽  
Pyramidal Neurons ◽  
Hippocampal Slices ◽  
Lipid Phase ◽  
Tissue Slices ◽  
Population Spikes ◽  
Afferent Volleys ◽  
Stimulation Of

Largo, Carlota, Geoffrey C. Tombaugh, Peter G. Aitken, Oscar Herreras, and George G. Somjen. Heptanol but not fluoroacetate prevents the propagation of spreading depression in rat hippocampal slices. J. Neurophysiol. 77: 9–16, 1997. We investigated whether heptanol and other long-chain alcohols that are known to block gap junctions interfere with the generation or the propagation of spreading depression (SD). Waves of SD were triggered by micro-injection of concentrated KCl solution in stratum (s.) radiatum of CA1 of rat hippocampal tissue slices. DC-coupled recordings of extracellular potential ( V o) were made at the injection and at a second site ∼1 mm distant in st. radiatum and sometimes also in st. pyramidale. Extracellular excitatory postsynaptic potentials (fEPSPs) were evoked by stimulation of the Schaffer collateral bundle; in some experiments, antidromic population spikes were evoked by stimulation of the alveus. Bath application of 3 mM heptanol or 5 mM hexanol completely and reversibly prevented the propagation of the SD-related potential shift (Δ V o) without abolishing the Δ V o at the injection site. Octanol (1 mM) had a similar but less reliably reversible effect. fEPSPs were depressed by ∼30% by heptanol and octanol, 65% by hexanol. Antidromic population spikes were depressed by 30%. In isolated, patch-clamped CA1 pyramidal neurons, heptanol partially and reversibly depressed voltage-dependent Na currents possibly explaining the slight depression of antidromic spikes and, by acting on presynaptic action potentials, also the depression of fEPSPs. Fluoroacetate (FAc), a putative selective blocker of glial metabolism, first induced multiple spike firing in response to single afferent volleys and then severely suppressed synaptic transmission (confirming earlier reports) without depressing the antidromic population spike. FAc did not inhibit SD propagation. The effect of alkyl alcohols is compatible with the idea that the opening of normally closed neuronal gap junctions is required for SD propagation. Alternative possible explanations include interference with the lipid phase of neuron membranes. The absence of SD inhibition by FAc confirms that synaptic transmission is not necessary for the propagation of SD, and it suggests that normally functioning glial cells are not essential for SD generation or propagation.

Filtration coefficient in cat hindlimb using protein concentration changes

1989 ◽  
Vol 256 (1) ◽  
pp. H186-H194 ◽  
Author(s):  
P. D. Watson ◽  
M. B. Wolf
Keyword(s):  
Protein Concentration ◽  
Venous Pressure ◽  
Filtration Coefficient ◽  
Volume Changes ◽  
Vascular Volume ◽  
Perfusate Flow ◽  
Wide Range ◽  
Concentration Changes ◽  
The Difference ◽  
Pentobarbital Sodium Anesthesia

The maximum value of capillary filtration coefficient (CFC) in maximally vasodilated cat skeletal muscle is disputed. It was hypothesized that the wide range of reported values was caused by the inability of gravimetric and volumetric measurements of tissue volume to separate transcapillary filtration from vascular volume changes. Consequently, we developed a method of measuring filtration rates from changes in venous protein concentration using Evan's blue-labeled albumin in the isolated hindlimb (pentobarbital sodium anesthesia). The filtration coefficient (PFFC) calculated from these filtration rates after a step in venous pressure should not be influenced by vascular volume changes. When the perfusate flow rate through the hindlimb was greater than 15 ml.min-1.100 g muscle-1, PFFC was 0.0085 +/- 0.0015 (SD, n = 8) ml.min-1.mmHg-1.100 g muscle-1. PFFC was observed to be unvarying from 1 to 12 min after the venous pressure elevation, in contrast to CFC values, which fall during the same period. It is argued that the difference between CFC and PFFC values is caused by vascular volume changes.

Local mechanisms of phase-dependent postsynaptic modifications of NMDA-induced oscillations in the abducens motoneurons: a simulation study

1996 ◽  
Vol 76 (2) ◽  
pp. 1015-1024 ◽  
Author(s):  
I. L. Kopysova ◽  
S. M. Korogod ◽  
J. Durand ◽  
S. Tyc-Dumont
Keyword(s):  
Synaptic Input ◽  
Pattern Generation ◽  
Ion Concentration ◽  
Extracellular Potassium ◽  
Pump System ◽  
Voltage Gated ◽  
Ion Concentrations ◽  
Concentration Changes ◽  
Transmembrane Currents

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.

scholarly journals Lowering of the extracellular Na+ concentration enhances high-K+-induced formation of inositol phosphates in the guinea-pig ileum

1988 ◽  
Vol 252 (3) ◽  
pp. 883-888 ◽  
Author(s):  
T Sasaguri ◽  
S P Watson
Keyword(s):  
Guinea Pig ◽  
Inositol Phosphates ◽  
Induced Response ◽  
Guinea Pig Ileum ◽  
Tissue Slices ◽  
Phospholipid Hydrolysis ◽  
Collagenase Treatment ◽  
High K ◽  
K Concentration ◽  
Dispersed Cells

1. Formation of inositol phosphates (InsPs) was measured in cross-chopped slices or dispersed cells, isolated by collagenase treatment, of guinea-pig ileum longitudinal smooth muscle pre-labelled with [3H]inositol. 2. Elevation of the extracellular K+ concentration by equimolar replacement of Na+ induced accumulation of InsPs in the dispersed cells and in the tissue slices. These effects were blocked by neither tetrodotoxin (1 microM) nor atropine (10 microM), and were approximately additive with carbachol-induced accumulation. 3. In the tissue slices, the response to K+ was partially inhibited by nifedipine (10 microM) and by CdCl2 (0.3 mM), but the carbachol-induced response was not altered. 4. Accumulation of InsPs induced by KCl-excess solution (high-K+ solution without Na+ replacement) was suppressed strongly by nifedipine and completely by CdCl2. The response to KCl excess was approx. 40% of that to high K+ with Na+ replacement. 5. Low-NaCl solution (replacement of NaCl with equimolar sucrose) also produced InsPs, and this was not blocked by either nifedipine (10 microM) or CdCl2 (0.3 mM). 6. The formation of InsPs by a maximally effective concentration of carbachol (1 mM) in the presence of KCl excess or low NaCl was greater than the additive effect of the two stimuli on their own. Enhancement of the carbachol-induced response by KCl excess disappeared in the presence of CdCl2 (0.3 mM). 7. These data suggest that formation of InsPs induced by high-K+ solution with equimolar replacement of Na+ consists of two components, i.e. high-K+-induced inositol-phospholipid hydrolysis by Ca2+ entry through voltage-sensitive channels, and low-Na+-induced formation of InsPs, insensitive to Ca2+ antagonists, but that both of them do not contribute significantly to the activation of phospholipase C by muscarinic stimuli.

scholarly journals Extracellular pH Changes and Accompanying Cation Shifts During Ouabain-Induced Spreading Depression

2000 ◽  
Vol 83 (3) ◽  
pp. 1338-1345 ◽  
Author(s):  
G. Menna ◽  
C. K. Tong ◽  
M. Chesler
Keyword(s):  
Spreading Depression ◽  
Cyclopiazonic Acid ◽  
Stratum Radiatum ◽  
Ph Changes ◽  
Alkaline Shift ◽  
Gradual Onset ◽  
High K ◽  
Ion Shifts ◽  
Free Media ◽  
Peak Value

Interstitial ionic shifts that accompany ouabain-induced spreading depression (SD) were studied in rat hippocampal and cortical slices in the presence and absence of extracellular Ca2+. A double-barreled ion-selective microelectrode specific for H+, K+, Na+, or Ca2+ was placed in the CA1 stratum radiatum or midcortical layer. Superfusion of 100 μM ouabain caused a rapid, negative, interstitial voltage shift (2–10 mV) after 3–5 min. The negativity was accompanied by a rapid alkaline transient followed by prolonged acidosis. In media containing 3 mM Ca2+, the alkalosis induced by ouabain averaged 0.07 ± 0.01 unit pH. In media with no added Ca2+ and 2 mM EGTA, the alkaline shift was not significantly different (0.09 ± 0.02 unit pH). The alkaline transient was unaffected by inhibiting Na+-H+ exchange with ethylisopropylamiloride (EIPA) or by blocking endoplasmic reticulum Ca2+ uptake with thapsigargin or cyclopiazonic acid. Alkaline transients were also observed in Ca2+-free media when SD was induced by microinjecting high K+. The late acidification accompanying ouabain-induced SD was significantly reduced in Ca2+-free media and in solutions containing EIPA. The ouabain-induced SD was associated with a rapid but relatively modest increase in [K+]o. In the presence of 3 mM external Ca2+, the mean peak elevation of [K+]o was 12 ± 0.62 mM. In Ca2+-free media, the elevation of [K+]o had a more gradual onset and reached a significantly larger peak value, which averaged 22 ± 1.1 mM. The decrease in [Na+]o that accompanied ouabain-induced SD was somewhat greater. The [Na+]o decreased by averages of 40 ± 7 and 33 ± 3 mM in Ca2+ and Ca2+-free media, respectively. In media containing 1.2 mM Ca2+, ouabain-induced SD was associated with a substantial decrease in [Ca2+]o that averaged 0.73 ± 0.07 mM. These data demonstrate that in comparison with conventional SD, ouabain-induced SD exhibits ion shifts that are qualitatively similar but quantitatively diminished. The presence of external Ca2+ can modulate the phenomenon but is irrelevant to the generation of the SD and its accompanying alkaline pH transient. Significance of these results is discussed in reference to the propagation of SD and the generation of interstitial pH changes.

scholarly journals Rapid Changes of Potassium Concentration at the Outer Surface of Exposed Single Neurons during Membrane Current Flow

1973 ◽  
Vol 61 (3) ◽  
pp. 385-399 ◽  
Author(s):  
E. Neher ◽  
H. D. Lux
Keyword(s):  
Potassium Concentration ◽  
Helix Pomatia ◽  
Membrane Current ◽  
Extracellular Potassium ◽  
Single Neurons ◽  
Extracellular Potassium Concentration ◽  
Quaternary Ammonium Ions ◽  
Concentration Changes ◽  
Snail Helix Pomatia ◽  
Short Time

K+-sensitive liquid ion-exchanger microelectrodes are shown to be capable of measuring concentration changes which occur on a millisecond time scale. However, some quaternary ammonium ions, such as tetraethylammonium and acetylcholine, are able to block electrode function when present in concentrations as low as 10-4 to 10-3 M. Changes in extracellular potassium concentration caused by spike activity or voltage clamp pulses of exposed single neurons of the snail Helix pomatia may be measured by these electrodes. Quantitative analysis shows that the total amount of excess potassium found in the vicinity of the cell a short time after a clamp pulse, is in relatively good agreement with the amount of potassium carried by the membrane current.

scholarly journals Ionic mechanisms in secretagogue-induced morphological changes in rat parotid gland.

1983 ◽  
Vol 97 (4) ◽  
pp. 1119-1130 ◽  
Author(s):  
B A Leslie ◽  
J W Putney
Keyword(s):  
Morphological Changes ◽  
Volume Density ◽  
Ultrastructural Changes ◽  
Tissue Slices ◽  
Vacuole Formation ◽  
High K ◽  
Ionic Mechanisms ◽  
Density Values ◽  
Depolarizing Agents ◽  
Rat Parotid

When 10(-5) M carbachol was added to parotid tissue slices incubated in buffer containing Ca++, watery vacuoles were formed in the cells. The percent volume density of vacuoles, as measured from 0.5-micron sections, increased from 0.64 +/- 0.15 SE (n = 7) to 3.09 +/- 0.99 (n = 5) in 10 min and, finally, to 7.27 +/- 1.88 (n = 4) in 30 min. In electron micrographs, most of the vacuoles appeared to arise from a location near the Golgi apparatus. Condensation of nuclear chromatin and a conformational change in mitochondria were also noted immediately after stimulation. The percent volume density values returned to basal levels with the addition of either 5 mM EGTA or 10(-6) M atropine after the addition of carbachol. Nuclei and mitochondria returned to normal configurations. In the presence of either 1 mM ouabain or high K+, or in the absence of added Ca++, carbachol failed to induce vacuole formation. However, low Na+ medium did not prevent the formation of vacuoles due to carbachol. Ultrastructural changes in nuclei and mitochondria were consistently associated with the appearance of vacuoles. Since both high K+ and ouabain blocked vacuole formation, it is unlikely that Na+ or K+ movements were important for the response. Rather, receptor-activated Ca++ influx, which is likely to be inhibited by depolarizing agents (such as high K+ or ouabain), is probably the more important factor in vacuole formation and other concomitant ultrastructural changes.

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