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T Brismar

Publications and source records attributed to T Brismar.

At least 37 records · Page 2Linked to original sources
PubMed1995

Physiology of transformed glial cells.

Much of our present knowledge of glial cell function stems from studies of glioma cell lines, both rodent (C6, C6 polyploid, and TR33B) and human (1321N1, 138MG, D384, R-111, T67, Tp-276MG, Tp-301MG, Tp-483MG, Tp-387MG, U-118MG, U-251MG, U-373MG, U-787MG, U-1242MG, and UC-11MG). New methods such as patch clamp and Ca2+ imaging have lead to rapid progress the last few years in our knowledge about glial cells, where an unexpected presence and diversity of receptors and ion channels have emerged. Basic mechanisms related to membrane potential and K+ transport and the presence of voltage gated ion channels (Na+, inwardly rectifying K+, Ca(2+)-activated K+, Ca2+, and Cl- channels) have been identified. Receptor function and intracellular signaling for glutamate, acetylcholine, histamine, serotonin, cathecolamines, and a large number of neuropeptides (bradykinin, cholecystokinin, endothelin, opioids, and tachykinins) have been characterized. Such studies are facilitated in cell lines which offer a more homogenous material than primary cultures. Although the expression of ion channels and receptors vary considerably between different cell lines and comparative studies are rare, a few differences (compared to astrocytes in primary culture) have been identified which may turn out to be characteristic for glioma cells. Future identification of specific markers for receptors on glial and glioma cells related to cell type and growth properties may have great potential in clinical diagnosis and therapy.

Amino Acids↗
PubMed1995

Subclinical nerve dysfunction in children and adolescents with IDDM.

The purpose of this study was to investigate whether young insulin-dependent diabetic patients still develop peripheral nerve dysfunction when using modern multiple insulin injection therapy and to elucidate if this correlated with various disease parameters. Seventy-five patients, 7 to 20 years old with a duration of diabetes of more than 3 years, and 128 age-matched healthy control subjects underwent bilateral studies of median, peroneal, and sural nerves. Presence of diabetes lowered motor conduction velocity (p < 0.0001), sensory conduction velocity (p < 0.0001) and sensory nerve action potential (p < 0.05) in all examined nerves. The mean change in conduction velocity induced by diabetes was -4.8 m/s in the peroneal nerve, -3.3 m/s in the median motor nerve, -2.6 m/s in the sural nerve and -2.4 m/s in the median sensory nerve. Fifty-seven percent of the patients had abnormal conduction (values outside 95% predictive interval) which was seen most often in the motor nerves, especially in the peroneal nerve (41%) followed by the median nerve (24%). In multiple regression analysis, long-term poor metabolic control and increased body length correlated with nerve dysfunction identified in most examined parameters. Three patients had signs or symptoms suggestive of neuropathy. It is concluded that despite modern multiple insulin injection therapy, with reasonably good metabolic control, nerve dysfunction is still common in children and adolescents with insulin-dependent diabetes mellitus. Risk factors are increased height and long-term poor metabolic control.

Adolescent↗
PubMed1995

Increased cation transport in mdr1-gene-expressing K562 cells.

Cation-transport properties were compared in a human leukemic cell line (K562) and its vincristine-selected, mdr1-gene-expressing sublines (K562/Vcr30 and K562/Vcr150) by the capacity of the cells to accumulate the potassium analogue thallium (201Tl). Determination of the time course of thallium accumulation in the absence and presence of ouabain, an inhibitor of sodium-potassium adenosine triphosphatase (ATPase), showed that the initial (at 20 min) rate of ouabain-resistant uptake was about 70% higher in the K562/Vcr30 cells than in the parental line. The maximal rate (Vmax) of ouabain-resistant uptake was 78 mmol/h for K562 cells and 115 mmol/h for K562/Vcr30 cells, and the Michaelis constant (Km) was 0.37 and 0.18 mmol, respectively. Bumetanide (50 microM), a specific inhibitor of ouabain-resistant Na-K-Cl cotransport, inhibited the elevated 201Tl uptake in K562/Vcr150 cells but had no effect on cellular vincristine accumulation. Incubation with different multidrug resistance (MDR)-reversing agents (verapamil as well as cyclosporin A and its analogue PSC833) had no significant effect on 201Tl uptake. Membrane depolarization by an elevation of the potassium concentration in the incubation medium did not affect vincristine accumulation in any cell line, which indicated that the changed drug-transport properties in mdr1-gene-expressing cells were not due to membrane hyperpolarization. It was concluded that P-glycoprotein-positive cells have a more efficient ouabain-resistant cation-transport mechanism than to cells without P-glycoprotein. A functional relationship between this phenomenon and MDR was not identified.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Effect of external K+, Ca2+, and Ba2+ on membrane potential and ionic conductance in rat astrocytes.

1. The purpose of this study was (a) to identify if astrocytes show a similar non-Nernstian depolarization in low K+ or low Ca2+ solutions as previously found in human glial and glioma cells, and (b) to analyze the influence of the K+ conductance on the membrane potential of astrocytes. 2. The membrane potential (Em) and the ionic conductance were studied with whole-cell patch-clamp technique in neonatal rat astrocytes (5-9 days in culture) and in human glioma cells (U-251MG). 3. In 3.0 mM K+ Em was -75 +/- 1.0 mV (mean +/- SEM, n = 39) in rat astrocytes and -79 +/- 0.7 mV (n = 5) in U-251MG cells. In both cell types Em changed linearly to the logarithm of [K+]0 between 3.0 and 160 mM K+ free medium caused astrocytes to hyperpolarize to -93 +/- 2.7 mV (n = 21) and U-251MG cells to depolarize to -27 +/- 2.1 mV (n = 3). 4. The I-E curve did not show inward rectification in astrocytes at this developmental stage. The slope conductance (g) exhibited only a small decrease (-19%) in K+ free solution and no significant change in 160 mM K+. 5. Ba2+ (1.0 mM) depolarized astrocytes to -45 +/- 2.9 mV (n = 11), decreasing the slope conductance (g) by 42.4 +/- 8.3% (n = 11). Ca2+ free solution depolarized astrocytes to -53 +/- 3.4 mV (n = 12) and resulted in a positive shift of the I-E curve, increasing g by 15.3 +/- 8.2% (n = 8). 6. Calculations indicated that a block of K+ channels explains the depolarizing effect of Ba2+. The effects of K+ free or Ca2+ free solutions on Em can be explained by a transformation of K+ channels to non-specific leakage channels. That astrocytes show a different reaction to low K+ than glioma cells can be related to the lack of inwardly rectifying K+ channels in astrocytes at this developmental stage.

Animals↗
PubMed1995

Mechanism of high K+ and Tl+ uptake in cultured human glioma cells.

1. The aim of this study was to elucidate if the K+ uptake was higher in cultured human glioma cells than in cells from other malignant tumors and to analyze the importance of membrane potential and K+ channels for the uptake. 2. K+ transport properties were studied with the isotopes 42K and the K-analogue 201Tl. 3. Comparison with cultured cells from other malignant tumors showed that the specific steady-state accumulation of Tl+ was significantly higher in glioma cells (U-251MG and Tp-378MG). 4. In Ringer's solution at 37 degrees C the rates of K+ and Tl+ uptake were both inhibited by about 55% in ouabain and 60% in furosemide, bumetanide, or Na(+)- or Cl(-)-free medium. This indicated that the routes for K+ and Tl+ uptake were similar and due to Na,K-ATPase-dependent transport and to Na-K-Cl cotransport. 5. About 10% of the uptake was neither ouabain nor bumetanide sensitive. Ba2+, which is known to block inward-rectifying K+ channels and to depolarize glial cells, and other K+ channel blockers (Cs+ and bupivacaine), had no effect on Tl+ uptake. 6. Metabolic inhibition with dinitrophenol reduced the uptake rate to 17%. 7. The washout of Tl+ was unaffected by bumetanide and K+ channel blockers, but dinitrophenol caused a transient increase of 75%, an effect which persisted in the presence of K+ channel blockers. 8. It was concluded that the high specific K+ and Tl+ accumulation in cultured human glioma cells was due not to the presence of inwardly rectifying K+ channels or other identified K+ channels, but to Na,K-ATPase dependent transport and Na-K-Cl cotransport.

Barium↗
PubMed1995

Normal values of nerve conduction in children and adolescents.

Healthy children and adolescents (n = 128) ranging in age from 6 to 20 years and in height from 114 to 193 cm underwent studies of median, peroneal and sural nerves bilaterally, including nerve conduction velocity, amplitude and motor distal latencies. Arms and legs were heated in all subjects to obtain skin temperatures around 34 degrees C. Both motor and sensory nerve conduction velocities were found to correlate more with height than with age. There was a strong negative correlation between height and peroneal conduction velocity (r = -0.40, P < 0.0001). On the contrary, a positive correlation was found between height and both median sensory (r = 0.30, P < 0.0001) and motor (r = 0.22, P < 0.001) conduction velocities. Skin temperature, even near 34 degrees C, had a strong effect on conduction velocity and motor distal latencies. It is concluded that consideration of height and temperature will improve the diagnostic safety of nerve conduction measurements in children and young adults.

Action Potentials↗
PubMed1994

Impaired recovery in diabetic rat nerve following anoxic conduction block.

It is well documented that diabetic rats and subjects have a paradoxical resistance to ischemic conduction block although the nerves of diabetes are more susceptible to entrapment neuropathies. The aim of the present study was to further analyze the effect of anoxia on the diabetic nerve. Nerve conduction was measured in vitro in desheathed sciatic nerves from spontaneously diabetic rats (BB-Wistar) and age-matched controls. After onset of anoxia the compound action potential (CAP) decreased to 50% in 17 min in diabetic rat nerves and 8 min in normals. Following reoxygenation CAP recovered to 50% in 30 s in normal rat nerves and after 3 min the recovery was 92%. In nerves from diabetic animals 50% recovery took 4 min, but still after 12 min CAP was suppressed to a 60% level of the original. Longer periods of anoxia did not impair the recovery in normal nerve as it did in the diabetic ones. This defective recovery after anoxia in nerves from diabetic animals may be relevant for the understanding of the pathogenesis of entrapment neuropathies in diabetic subjects.

Action Potentials↗
PubMed1994

A method for analysis of cellular K-transport mechanisms through thallium (201Tl) uptake in human lymphocytes.

Thallium (Tl) is the K-congener with the highest specific affinity to K-binding sites and the largest permeability in K-channels, and its usefulness for analysis of cellular K-transport mechanisms was investigated. The uptake of 201Tl was measured in cultured human lymphocytes (Jurkat cells and EBV-transformed B-cells) after various incubation conditions. In a complete culture medium the half-time of the Tl-uptake was 10 min at 37 degrees C and the steady state accumulation ratio (intracellular/extracellular) was c. 50. The steady state ouabain sensitive uptake was 81% in complete culture medium, it was reduced after substitution with Ringer solution and by a decrease in temperature (from 37 to 22 degrees C). The ouabain resistant uptake was higher at 22 degrees C than at 37 degrees C and it was almost completely inhibited in Na-free or Cl-free solution and by furosemide. The present results indicate that there are only two major routes for K-uptake in lymphocytes and that 201Tl may be a useful substitute for K in the analysis of cellular K-transport mechanisms.

B-Lymphocytes↗
PubMed1993

Effect of external cation concentration and metabolic inhibitors on membrane potential of human glial cells.

1. The effect on membrane potential (Em) of low external [K+]o, [Na+]o and [Ca2+]o and of metabolic inhibitors was studied in cultured human glial cells (U-787CG) and human glioma cells (Tp-483MG and U-251MG). Whole cells were voltage or current clamped with the tight-seal recording technique. 2. Em was -76 and -80 mV in glial and glioma cells (mean values in U-787CG and U-251MG, respectively) in a reference external solution with 3.0 mM K+. K(+)-free external solution caused a rapid and reversible depolarization of these cells by about 26 and 42 mV (respectively). 3. Block of K+ channels with 1 mM Ba2+ in external solution rapidly depolarized the cells (U-251MG) by about 35 mV. 4. Na(+)-free solutions caused a delayed depolarization by 40-50 mV, which was slowly reversible (in 2 min). 5. Ouabain (1 mM) depolarized the cells by about 4 mV. It did not prevent the effect of K(+)-free solution. 6. Ca(2+)-free external solution rapidly depolarized the cells to Em about -17 mV. The combination of either Na(+)-K(+)-free or Na(+)-Ca(2+)-free solution transiently repolarized the cell, which indicated that the K+ selectivity of the membrane was decreased in both K(+)- and Ca(2+)-free solutions. 7. Metabolic inhibitors (carbonyl cyanide p-trifluoromethoxy-phenylhydrazone (FCCP) and 2,4-dinitrophenol (DNP)) rapidly and reversibly depolarized the cells. This effect was not prevented by intracellular perfusion of a strong Ca(2+)-buffering solution. 8. Voltage clamp revealed only minor changes (< 20%) in the leak conductance (g) of cells that were depolarized by the above-mentioned solutions. 9. Positive polarizing current elicited (in some cells) a regenerative depolarization. The threshold for depolarization was less in low external [K+]o. 10. It is concluded (a) that the resting potential of these glial cells depends on ion channels that are K+ selective only in the presence of external Ca2+ and K+ and (b) that this K+ selectivity may require that Em is near the reversal potential for potassium (EK), and (c) that the action of metabolic inhibitors (DNP and FCCP) is different from that in neurones.

2,4-Dinitrophenol↗
PubMed1992

Nerve conduction in the hands of vibration exposed workers.

Symptoms of peripheral neuropathy in the hands are common among workers using vibrating tools. The mechanism for this and its relation to carpal tunnel syndrome (CTS) was studied in workers exposed to vibration at their workplace (17), along with a control group of healthy construction workers with heavy manual work but without vibration exposure (10). Patients with uni- or bilateral CTS (11) and a group of healthy volunteers without manual work (9) were included for comparison. Median nerve conduction velocities were measured both over the carpal tunnel and in a more distal segment. Vibration exposed workers had similar conduction velocities to unexposed construction workers. The subgroup of vibration exposed patients with symptoms from the hands had normal conduction in the ulnar nerve but demonstrated a decrease in median nerve conduction comparable (but less pronounced) with the CTS group. On a group basis these results indicated that the median nerve is most vulnerable for hand-arm vibrations. However, the conduction defects were not pronounced enough to diagnose CTS in most individual cases.

Adult↗
PubMed1991

Mechanism of anoxic conduction block in mammalian nerve.

The mechanism by which anoxia blocks impulse conduction was studied in isolated sciatic nerves from the rat. The desheathed nerve was mounted in a recording chamber, and the compound action potential (CAP) was measured at controlled temperature (23 and 37 degrees C). When the nerve was irrigated with nitrogenated Ringer's solution compound action potential decreased to 50% in 10 min at 37 degrees C and in 35 min at 23 degrees C, whereas in oxygenated solution compound action potential decreased less than 5% in 60 min. A Na-free nitrogenated solution similarly caused anoxic block, that is the effect was independent of impulse activity. Ouabain (1 mM) decreased compound action potential by only ca. 4% in 30 min, and the effect of anoxia was delayed in presence of ouabain. Dinitrophenol (0.05 mM) reduced compound action potential to 50% in 5 min. These findings indicated that the anoxic block was not related to changes in axonal concentration of Na or K following impulse activity or inhibition of Na-K-ATPase. Instead the findings imply that the anoxic block is due to inactivation of Na-channels as a consequence of inhibition of another ATP-dependent process in the axon.

Action Potentials↗
PubMed1991

In vivo analysis of intracellular thallium-201 accumulation in skeletal muscle of the rat.

The specific accumulation of the K(+)-analogue Tl+ (201Tl+) in muscle after intramuscular injection was analysed by gamma spectrometry in vivo of rat hamstring muscles. A mixture (0.1 ml) of 201Tl+ (thallous+ chloride-) and 99mTc-pertechnetate- (Na+ pertechnetate-) was given, by which 99mTc-pertechnetate- served as a reference substance with negligible intracellular accumulation. After 30 min 8.9 +/- 5.8% of injected 99mTc-pertechnetate- remained in the muscle and 49 +/- 10% of 201Tl+ (+/- SD, n = 18). The difference between 201Tl+ and 99mTc-pertechnetate- at 30 min was taken as a measure of the intracellular 201Tl+ accumulation, which was 40% of the initial amount of 201Tl+. The half-time of the calculated intracellular 201Tl+ accumulation was 4.9 +/- 1.9 min. In the presence of ouabain (1.0 mM in the injectate) the intracellular 201Tl+ accumulation was 25 +/- 10% (n = 7), that is ouabain decreased the intracellular 201Tl+ accumulation by 38% (P = 0.0035). Non-radioactive Tl+ (1.0 mM Tl-acetate in the injectate) inhibited the uptake by 35% (P = 0.0013). Ouabain did not significantly affect the half-time for the Tl+ uptake. An increase in [K+] of the injectate from 0 to 5 mM had no significant effect. Insulin (0.2 units in the injectate) had no effect. It is concluded that the specific Tl(+)-accumulating properties of muscle fibres can be studied with the present in vivo technique, which can provide information about the Na-K-ATPase activity and the membrane potential of muscle fibres.

Animals↗
PubMed1990

Hearing loss from the acoustic artifact of the coil used in extracranial magnetic stimulation.

The stimulating coil used in extracranial magnetic field stimulation (EMFS) emits a high intensity impulse sound artifact that causes permanent threshold shifts in the unprotected ears of experimental animals. At magnetic stimulation levels of 50 to 100%, the magnetic coil acoustic artifact (MCAA) ranged from 145 to 157 dB peak sound pressure level at the eardrum. The magnetic field alone did not appear to cause hearing impairment since no threshold shifts were observed in ears that were plugged with ear protectors during exposure to the MCAA. These findings suggest that the acoustic artifact produced by EMFS in the clinic may pose some risk for hearing loss in patients and clinicians when held in close proximity to the unprotected ear. We recommend the use of ear protectors for the patient and clinician during EMFS as a precautionary measure to prevent hearing loss.

Animals↗
PubMed1989

Thallium-201 uptake relates to membrane potential and potassium permeability in human glioma cells.

The mechanism for 201Tl+ uptake was studied in cultured human glioma cell lines. Ouabain (1 mM) decreased the uptake at steady-state to 60%, but the rate of uptake was faster in the presence of ouabain. Addition of non-radioactive Tl+ (to a K+-free medium) decreased the uptake, but much less than expected for a system limited by the number of transport sites. Changes in K+ concentration of incubation medium affected the 201Tl+ uptake as predicted by the electrochemical equilibrium (Nernst equation). Using the uptake in isotonic KCl as a reference for membrane potential (0 mV), the calculated membrane potential was -75 mV in a medium with 3.0 mM K+. The Tl+-flux constants and the membrane permeabilities for Tl+ and K+ were calculated from the rate of uptake and from wash-out experiments. This is a new method for membrane potential and permeability studies in cell populations. The mechanism for 201Tl+ uptake is relevant for the clinical interpretation of 201Tl+ scintigraphy.

Humans↗
PubMed1989

[Cellular mechanisms in diabetic neuropathy].

Although the pathogenesis of distal diabetic neuropathy is still uncertain, a possible mechanism might be postulated on the basis of results of several experimental studies. Differences between animal and human models are obvious--especially with regard to the time factor, but in attempts at elucidating basic mechanisms use can be made of the close resemblance between animal and human nerve fibres at the cellular and molecular level. A decrease in sodium potassium ATPase activity, causing intracellular accumulation of oxidised sodium, cellular oedema, and myelin detachment around the nodes of Ranvier, would seem to be the central component in the pathogenesis.

Adenosine Triphosphatases↗
PubMed1989

Inward rectifying potassium channels in human malignant glioma cells.

Human glioma cells obtained from established cell lines (Tp-276MG, Tp-301MG, Tp-378MG, Tp-483MG and U-251MG) were analyzed for the presence of ion channels with the tight-seal voltage clamp technique. The current-voltage relation revealed a marked inward rectification at hyperpolarizing voltages, due to the presence of inward rectifying K-channels in cells from all studied cell lines. These channels were conducting when the membrane potential was more negative than the K-equilibrium potential. The slope conductance for the inward K-currents (gKi) was affected both by [K+]i and [K+]o. gKi was proportional to [K+]o raised to 0.35 or 0.50, of which the larger value was measured in the presence of low [K+]i (25 mM). The rectification was not significantly different in cells perfused with Mg-free EDTA-buffered internal solution. Tl+ was 3.5 times more permanent than K+. gKi was blocked by Cs+ (1 mM) in a voltage-dependent way (more effective in the hyperpolarized membrane), and by Na+ (154 mM) depending on voltage and time. From measurements of unitary current events in membrane patches (outside out or cell attached) the conductance of the single inward rectifying channel was estimated to be 27 +/- 7 pS. This type of ion channel may be important for K-uptake by glial cells and hence for the K-homeostasis in the brain.

4-Aminopyridine↗
PubMed1989

Potassium and sodium channels in human malignant glioma cells.

Human malignant glioma cells from 5 different cell lines were voltage clamped and examined for the presence of depolarization-activated ion channels. Outward K-currents were elicited at membrane potentials greater than 40 mV, which had two main components, one which was delayed and blocked by externally applied tetraethylammonium (TEA, 10 mM), and another which was instantaneous and insensitive to TEA in the outside solution. The proportion of the two K-current components varied between cell lines. An increase in [Ca2+]o in the range 0-4 mM, decreased the leak conductance and shifted the activation of the instantaneous outward K-current towards more positive potentials. Mg2+, Zn2+ and Co2+ had qualitatively similar effects. Patch recordings with 150-160 mM K+-solution on both sides of the membrane revealed that the delayed outward K-current was carried through large conductance (250-300 pS) channels. Changes in free [Ca2+]i from 0 to 2 x 10(-8) M increased the activation of the large conductance K-channel. Small Na-currents were identified in cells from one cell line (Tp-378MG). The Na-conductance ranged from 0.5 to 7.5 nS in 25% of the cells, and was less than 0.5 nS in 75%. The Na-channels were activated and inactivated at 30-40 mV more positive potentials than in the mammalian peripheral nerve. Tetrodotoxin (100 nM) blocked gNa almost completely.

4-Aminopyridine↗