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W Raabe

Publications and source records attributed to W Raabe.

At least 19 recordsLinked to original sources
PubMed1992

Ammonium ions abolish excitatory synaptic transmission between cerebellar neurons in primary dissociated tissue culture.

1. Transmitter glutamate is thought to be derived from glutamine via cleavage by glutaminase. NH+4 inhibits glutaminase. Therefore the decrease of glutamatergic excitatory synaptic transmission by NH+4 was thought to be due to the inability of glutamine to serve as precursor for glutamate. However, in cat spinal cord, NH+4 abolished excitatory synaptic transmission by a conduction block for action potentials in presynaptic terminals. The conduction block prevented inferences as to the effects of NH+4 on the availability of glutamate for synaptic transmission. This study reexamines the effects of NH+4 on glutamatergic excitatory synaptic transmission in cerebellar neurons in tissue culture. 2. Whole-cell patch voltage-clamp recordings were obtained from presumed Purkinje cells. Extracellular stimulation of presumed granule cells produced mono- and polysynaptic excitatory postsynaptic currents (EPSCs). In addition, presumed Purkinje cells showed spontaneous EPSCs that occurred independently of the addition of tetrodotoxin (TTX) or Cd2+ to the extracellular solution. 3. NH+4 (5-10 mM) abolished evoked mono- and polysynaptic EPSCs without abolishing spontaneous EPSCs and without significant effects on action currents in the Purkinje cell soma. 4. Increase of K+ in the extracellular solution to 10-12 from 5 mM abolished evoked EPSCs without abolishing spontaneous EPSCs and without significant effects on action currents in the Purkinje cell soma. 5. Mixtures of NH+4 and K+, with each ion in a concentration insufficient to affect evoked EPSCs when given alone, abolished evoked EPSCs when the sum of NH+4 and K+ exceeded 10-12 mM. 6. Increase of intracellular pH by trimethylamine had no effect on evoked and spontaneous EPSCs.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1990

Effects of NH4+ on reflexes in cat spinal cord.

1. In deeply barbiturate-anesthetized animals. NH4+ decreases spinal excitatory synaptic transmission by neuronal depolarization and subsequent block of conduction of action potentials into presynaptic terminals of low-threshold (presumably Ia-) afferents. Because barbiturates by themselves depress excitatory synaptic transmission and may have modified the effects of NH4+, this study examines the effect of NH4+ on excitatory synaptic transmission in the unanesthetized animal. 2. The effects of NH4+ on monosynaptic and polysynaptic excitatory reflexes as well as di- and polysynaptic inhibition were investigated in the spinal cord of the decerebrate and unanesthetized cat in vivo. 3. The monosynaptic excitatory reflex (MSR) elicited by muscle nerve stimulation and polysynaptic excitatory reflexes elicited by muscle (MSR-PSR) or cutaneous nerve stimulation (Cut-PSR) were recorded from the ventral roots L7 or S1. The P-wave was recorded from the cord dorsum. Di- and polysynaptic inhibition was elicited by muscle nerve stimulation and measured as decrease of the MSR. 4. Intravenous infusion of ammonium acetate (AA) decreased MSR and the monosynaptic motoneuron pool excitatory postsynaptic potential (EPSP) recorded from the ventral root (VR-EPSP). Decrease of MSR and VR-EPSP was accompanied by an increase of the intraspinal conduction time in presynaptic terminals. The maximal decrease of the MSR was preceded by a period of transient increase of the MSR and reflex discharges from previously subthreshold VR-EPSPs. 5. The effects of NH4+ on MSR and VR-EPSP are consistent with those in barbiturate-anesthetized animals and suggest that NH4+ also decreases monosynaptic excitation in unanesthetized animals by depolarization and subsequent conduction block for action potentials in presynaptic terminals. 6. Decrease of the MSR was accompanied by a decrease of the P-wave, indicating that NH4+ simultaneously decreases mono- and oligosynaptic excitatory synaptic transmission as well as presynaptic inhibition. 7. Decrease of the MSR was accompanied by increases of MSR-PSR and Cut-PSR and decreases of di- and polysynaptic postsynaptic inhibition. 8. The neuronal circuits underlying MSR-PSR and Cut-PSR include presynaptic inhibition of group I and II afferents as well as postsynaptic inhibition of motoneurons. It is suggested that increases of MSR-PSR and Cut-PSR are contributed to by decreases of pre- and postsynaptic inhibition and neuronal depolarization by NH4+. These effects increase afferent input to motoneurons, permit uncontrolled discharge of motoneurons, and initiate reflex discharges by previously subthreshold excitatory postsynaptic potentials.

Acetates↗
PubMed1989

Ammonium decreases excitatory synaptic transmission in cat spinal cord in vivo.

1. Glutamine is thought to be a precursor of the pool of glutamate that is used as synaptic transmitter. NH4+ inhibits glutaminase, the enzyme presumed to cleave glutamine into glutamate in synaptic terminals. Therefore a decrease by NH4+ of excitatory synaptic transmission in hippocampus was suggested to be due to the inability to utilize glutamine as a precursor for glutamate and subsequent transmitter depletion. This study reexamines the effects of NH4+ on excitatory synaptic transmission. 2. The effects of NH4+ on excitatory synaptic transmission from low-threshold afferent fibers, presumably Ia-afferent fibers, to motoneurons was investigated in the spinal cord of anesthetized cats in vivo. 3. Action potentials of low-threshold afferent fibers were recorded at the entry of the dorsal roots into the spinal cord. An extracellular electrode within a motoneuron nucleus recorded the action potential of low-threshold afferent fibers and the extracellular monosynaptic excitatory postsynaptic potential, i.e., the focal synaptic potential (FSP). This extracellular electrode also recorded the antidromic field potential (AFP) in response to ventral root stimulation. Electrodes on the ventral roots recorded the monosynaptic reflex (MSR) and the monosynaptic excitatory postsynaptic potential in motoneurons electrotonically conducted into the ventral roots (VR-EPSP). 4. Intravenous infusion of ammonium acetate (AA) reversibly decreased MSR, VR-EPSP, and FSP, i.e., decreased excitatory synaptic transmission. 5. The decrease of VR-EPSP and FSP was accompanied initially by a decrease of conduction and, eventually, a conduction block in presynaptic terminals of low-threshold afferent fibers. 6. The decreases of VR-EPSP and FSP were also accompanied by the transient appearance of a reflex discharge, triggered by VR-EPSPs of decreased amplitude, and changes of the AFP indicating increased invasion of motoneuron somata by antidromic action potentials. 7. It is suggested that NH4+ depolarizes intraspinal Ia-afferent fibers and motoneurons. This depolarization initially decreases and then blocks conduction of action potentials into the presynaptic terminals of Ia-afferent fibers. The conduction block prevents the release of excitatory transmitter and decreases excitatory synaptic transmission. 8. The suggested depolarizing action of NH4+ may be due to K+-like ionic properties of NH4+ and/or an inhibition of K+-uptake into astrocytes. 9. The conduction block in presynaptic terminals of low-threshold afferent fibers can fully explain the decrease of excitatory synaptic transmission by NH4+. Because of the conduction block in presynaptic terminals, this study does not permit a conclusion as to an inhibition by NH4+ fo the utilization of glutamine as a precursor for glutamate used as synaptic transmitter.

Action Potentials↗
PubMed1987

The H-reflex in the encephalopathy due to ammonia intoxication.

Ammonia intoxication has been shown to decrease excitatory synaptic transmission in several regions of the central nervous system. To investigate the relation between an effect of ammonia on excitatory synaptic transmission and the behavioral depression in the encephalopathy due to ammonia intoxication, this study examined in the rat the effects of ammonia intoxication on the H-reflex, the behavioral and neurological signs of the encephalopathy due to ammonia intoxication, and correlated the effects on the H-reflex with the signs of encephalopathy. Ammonia intoxication abolished the H-reflex without affecting the M-response. This indicated that ammonia intoxication decreased spinal excitatory synaptic transmission without affecting neuromuscular excitatory synaptic transmission. In the encephalopathy due to ammonia intoxication, the H-reflex disappeared only during a very advanced stage of behavioral depression, i.e., coma. During early stages of behavioral depression, i.e., during a decrease of reactions to sensory stimuli, the H-reflex was not affected by ammonia intoxication. Therefore, mechanisms other than a decrease of excitatory synaptic transmission in the central nervous system may be responsible for the behavioral depression seen in early stages of the encephalopathy due to ammonia intoxication.

Action Potentials↗
PubMed1985

Pathophysiology of ammonia intoxication.

Ammonia intoxication affects postsynaptic inhibition and disturbs inhibitory neuronal interactions. This study investigated whether or not the effect of ammonia on postsynaptic inhibition was associated with a change of the EEG, i.e., a change in the function of the central nervous system such as in an encephalopathy. We showed that the effect of ammonia on postsynaptic inhibition was associated with a marked change of the EEG, and that this change was not due to an effect of ammonia on the brain stem reticular activating system. In addition, it was shown that in the central nervous system a NH+4 concentration of about 1 mumol/g affected postsynaptic inhibition. Because ammonia simultaneously affected postsynaptic inhibition and the EEG at a NH+4 tissue concentration comparable to that observed in encephalopathy, it is proposed that a dysfunction of postsynaptic inhibition caused the encephalopathy due to ammonia intoxication by simultaneously disturbing inhibitory neuronal interactions in many regions of the central nervous system.

Acetates↗
PubMed1985

Porta-caval shunting changes neuronal sensitivity to ammonia.

The relations between an effect of ammonia on postsynaptic inhibition, the amount of ammonium acetate i.v. to obtain this effect, and the tissue concentrations of NH4+ and glutamine were investigated in the cerebral cortex of cats without and with portacaval shunts. Normal cats required 2.43 mmol/kg ammonium acetate to affect postsynaptic inhibition. Cerebral NH4+ and glutamine increased from 0.21 mumol/g to 0.77 mumol/g and from 2.92 mumol/g to 5.54 mumol/g, respectively. In portacaval shunted cats, postsynaptic inhibition was normal in spite of increases of NH4+ and glutamine to 1.37 mumol/g and 14.28 mumol/g, respectively. Only 0.7 mmol/kg of ammonium acetate were sufficient to affect postsynaptic inhibition. This was associated with a statistically insignificant increase of NH4+ to 1.61 mumol/g and no change of glutamine. A chronic portasystemic shunt markedly increases the tolerance of postsynaptic inhibition to NH4+. However, postsynaptic inhibition becomes very sensitive to an acute systemic ammonia load and the associated increase of tissue NH4+ in the cerebral cortex. These observations help to understand the pathogenesis of the encephalopathy precipitated in patients with portasystemic shunts by an acute systemic ammonia load such as resulting from a gastrointestinal hemorrhage.

Acetates↗
PubMed1985

Ammonia intoxication: effects on cerebral cortex and spinal cord.

The effect of an acute systemic ammonia intoxication on the metabolic states of the cerebral cortex and the spinal cord of the same animal was studied in the cat. The intravenous infusion of ammonium acetate (2 and 4 mmol/kg body weight/30 min) increased the gross levels of tissue NH4+, glutamine, glutamine/glutamate ratio, lactate, and the lactate/pyruvate ratio in the cerebral cortex and the spinal cord. Pyruvate increased, but significantly only in the spinal cord; aspartate decreased, but significantly only in the cerebral cortex. The infusion of ammonium acetate did not significantly change the levels of phosphocreatine, ATP, ADP, AMP, total adenine nucleotides, adenylate energy charge, glucose, glutamate, alpha-ketoglutarate, and malate in either tissue. The changes of NH4+, glutamine, and lactate levels as well as glutamine/glutamate and lactate/pyruvate ratios in the spinal cord correlated significantly with the corresponding changes of these metabolites in the cerebral cortex. Thus, cerebral cortex and spinal cord show certain specific and comparable metabolic changes in response to a systemic ammonia intoxication. The effect of ammonia intoxication on the increases of glutamine and lactate levels is discussed.

Acetates↗
PubMed1984

Ammonia, postsynaptic inhibition and CNS-energy state.

Ammonia intoxication decreases the hyperpolarizing action of postsynaptic inhibition. This study examines the metabolic state of the spinal cord during this effect of ammonia intoxication on spinal motoneurons. ATP, ADP, AMP, the adenylate energy charge, glucose, PCr, pyruvate, alpha-ketoglutarate and glutamate were unchanged during the effect of ammonia on the hyperpolarizing action of postsynaptic inhibition. NH4+, glutamine and lactate were increased. Ammonia intoxication affected postsynaptic inhibition without changes of the resting membrane potential, the neuron input resistance, the action potential and EPSPs. The encephalopathy caused by ammonia intoxication is known to occur without an alteration of the tissue energy state. The effect of ammonia intoxication on postsynaptic inhibition can be considered as a cause of the encephalopathy because postsynaptic inhibition is altered without a change of the tissue energy state, the resting membrane potential, the whole neuron resistance, the action potential and EPSPs.

Ammonia↗
PubMed1983

Ammonia intoxication and hyperpolarizing postsynaptic inhibition.

Systemic ammonia intoxication abolished the hyperpolarizing action of postsynaptic inhibition in the CNS at tissue concentrations of NH+4 which are sufficient to produce the earliest signs of encephalopathy. Therefore, the action of NH+4 on hyperpolarizing postsynaptic inhibition has to be considered as the cause, or as a contributing cause, of the encephalopathy due to systemic ammonia intoxication.

Ammonia↗
PubMed1977

Anticonvulsant action of diazepam: increase of cortical postsynaptic inhibition.

The action of intravenously administered diazepam (Valium) on postsynaptic inhibition was studied in cat motor cortex. The efficacy of postsynaptic inhibition of pyramidal tract cells was measured as the ability to suppress action potential generation. Diazepam increased the suppression of action potentials by inhibition. This effect may explain the anticonvulsant action of diazepam.

Action Potentials↗
PubMed1976

[Thyroid hormones and thyrotropin in liver and kidney insufficiency].

In 22 patients with hepatic or renal insufficiency the serum concentrations of trijodothyronin, thyroxine and thyrotropin and also the T4-binding capacity of TBG were determined. The mean serum T3 concentration was found to be significantly lower in patients with hepatic coma when compared with euthyroid subjects. In the cases of renal insufficiency the serum T3 concentrations were in the normal range. Due to hormone loss through dialysis however, the mean value of the T3 concentrations was slightly lower than the average concentration of normal subjects. The obtained results agree with those of our earlier studies which showed that there are significant differences between liver artery and vein T3 concentrations in serum, whereas no such differences could be ascertained between serum concentrations in renal artery and vein. On the basis of these findings it is assumed that conversion of T4 into T3 occurs predominantly in the liver.

Hepatic Encephalopathy↗
PubMed1975

Disinhibition in cat motor cortex by ammonia.

The effect of intravenously administered ammonium salts on postsynaptic inhibition of pyramidal tract cells was investigated in cat motor cortex. Extracellular recordings revealed that pyramidally or thalamically mediated inhibition of antidromic action potentials is abolished by ammonia. Intracellular recordings demonstrated that hyperpolarizing IPSPs vanished and EPSPs appeared while the inhibitory stimuli still triggered a decrease of neuronal resistance and the resting membrane potential was unchanged. It is concluded that ammonia disinhibited action-potential generation and EPSPs by shifting E(IPSP) to the level of the resting membrane potential. With disinhibition and facilitation replacing inhibitation of action potentials, ammonia clearly disturbs those cortical functions involving postsynaptic inhibition.

Ammonia↗