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R Mager

Publications and source records attributed to R Mager.

At least 19 recordsLinked to original sources
PubMed1995

GTP- and GDP-analogues modulate an inwardly rectifying chloride channel in cultured hippocampal neurons.

Three different GABA-insensitive Cl- channels could be resolved in cultured hippocampal neurons using the inside-out patch clamp configuration. The most commonly observed channel revealed an inward rectification with a chord conductance of 40 pS in symmetrical Cl- solutions at a membrane potential of -50 mV and had voltage sensitive gating kinetics. Channel openings were not observed in cell-attached patch, and after excision, several minutes of perfusion of the cytoplasmic side were required before detecting the first openings. The open state probability was increased by guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S 10(-4) M) and reduced by guanosine 5'-O-(2-thiophosphate) (GDP-beta-S 10(-4) M) suggesting its regulation by G proteins. This new identified chloride channel may account for the previously described voltage-sensitive, inward-rectifying whole cell Cl- current which was enhanced by adenosine in a pertussis toxin-sensitive manner.

Animals↗
PubMed1994

Prevention of Ca(2+)-mediated action potentials in GABAergic local circuit neurones of rat thalamus by a transient K+ current.

1. Neurones enzymatically dissociated from the rat dorsal lateral geniculate nucleus (LGN) were identified as GABAergic local circuit interneurones and geniculocortical relay cells, based upon quantitative analysis of soma profiles, immunohistochemical detection of GABA or glutamic acid decarboxylase, and basic electrogenic behaviour. 2. During whole-cell current-clamp recording, isolated LGN neurones generated firing patterns resembling those in intact tissue, with the most striking difference relating to the presence in relay cells of a Ca2+ action potential with a low threshold of activation, capable of triggering fast spikes, and the absence of a regenerative Ca2+ response with a low threshold of activation in local circuit cells. 3. Whole-cell voltage-clamp experiments demonstrated that both classes of LGN neurones possess at least two voltage-dependent membrane currents which operate in a range of membrane potentials negative to the threshold for generation of Na(+)-K(+)-mediated spikes: the T-type Ca2+ current (IT) and an A-type K+ current (IA). Taking into account the differences in membrane surface area, the average size of IT was similar in the two types of neurones, and interneurones possessed a slightly larger A-conductance. 4. In local circuit neurones, the ranges of steady-state inactivation and activation of IT and IA were largely overlapping (VH = 81.1 vs. -82.8 mV), both currents activated at around -70 mV, and they rapidly increased in amplitude with further depolarization. In relay cells, the inactivation curve of IT was negatively shifted along the voltage axis by about 20 mV compared with that of IA (Vh = -86.1 vs. -69.2 mV), and the activation threshold for IT (at -80 mV) was 20 mV more negative than that for IA. In interneurones, the activation range of IT was shifted to values more positive than that in relay cells (Vh = -54.9 vs. -64.5 mV), whereas the activation range of IA was more negative (Vh = -25.2 vs. -14.5 mV). 5. Under whole-cell voltage-clamp conditions that allowed the combined activation of Ca2+ and K+ currents, depolarizing voltage steps from -110 mV evoked inward currents resembling IT in relay cells and small outward currents indicative of IA in local circuit neurones. After blockade of IA with 4-aminopyridine (4-AP), the same pulse protocol produced IT in both types of neurones. Under current clamp, 4-AP unmasked a regenerative membrane depolarization with a low threshold of activation capable of triggering fast spikes in local circuit neurones.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Nitric oxide controls oscillatory activity in thalamocortical neurons.

Nitric oxide (NO) is considered a diffusible messenger involved in neuronal communication, although the post-synaptic target cells of NO action and the associated biological function in the CNS are still a matter of controversy. Within the discrete pattern of NO-synthesizing neurons in the brain, NO synthase is specifically colocalized with the cholinergic brain stem-thalamic system, which is thought to regulate the state-dependent activity of the thalamocortical circuit. Here we report evidence indicating that the release of NO onto thalamocortical neurons results in an alteration in voltage dependence of the hyperpolarization-activated cation conductance, probably mediated via the cGMP system. NO selectively dampens oscillatory neuronal activity, indicating a rapidly diffusing signaling mechanism that controls the functional state of the thalamocortical network.

Animals↗
PubMed1991

Pharmacological blockade of Cl- pumps or Cl- channels reduces the adenosine-mediated depression of stimulus train-evoked Ca2+ fluxes in rat hippocampal slices.

Stimulus train-evoked decreases of the extracellular Ca2+ concentration (delta Ca) were measured with ion-sensitive electrodes in the CA1 area of rat hippocampal slices. The adenosine receptor antagonist, theophylline, led to a marked increase of delta Ca in the synaptic and in the soma layer reflecting an increased activation and enhanced frequency potentiation of pyramidal neurons in the absence of endogenous adenosine action. The theophylline effect was significantly reduced in the presence of the C1 channel blocker, 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS) or of the Cl- pump blocker, furosemide. The data indicate that the adenosine-mediated modulation of the repetitive input strength is related to the function of Cl- ions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

HIV-1 Nef protein exhibits structural and functional similarity to scorpion peptides interacting with K+ channels.

The persistent infection of human glial cells with HIV-1 is characterized by prominent expression of the Nef protein. In order to evaluate the possible role of Nef in the development of HIV-1-associated neurological disorders, we compared Nef with known neuroactive proteins. We found that HIV Nef shares sequence and structural features with scorpion peptides known to interact with K+ channels. Sequence similarity encompasses two distinct regions of scorpion peptides. Based on crystallography data, both regions in scorpion peptides cooperate in forming a common domain stabilized by ion pairs between charged amino-acid residues. Recombinant Nef protein, as well as a synthetic part of a scorpion channel active peptide (M10), reversibly increased the total K+ current of chick dorsal root ganglions in patch-clamp experiments without killing the cells. These results indicate that a region conserved in HIV Nef and scorpion peptides concurs in both structure and electrophysiological activity and suggest that Nef, like scorpion peptides, may affect neuronal cell function.

Amino Acid Sequence↗
PubMed1990

Adenosine modulates a voltage-dependent chloride conductance in cultured hippocampal neurons.

Whole cell currents were recorded in cultured rat hippocampal neurons using the patch-clamp method. When the cells were held near the resting membrane potential (-60 mV) the application of adenosine (1 microM) or the adenosine analogues 2CA (100 nM) and R-PIA (40 nM) induced a steady-state inward current. This response was unchanged when extra- and intracellular media were used, in which Na+ and K+ were substituted by impermeable ions in equimolar concentrations. In contrast the current was affected by lowering the extracellular Cl- concentration and thus Cl- was considered to be the ionic carrier. Additionally an almost complete block of the current was observed after applications of DIDS (50 microM), a putative Cl- channel blocker. The modulated current was voltage-dependent and was slowly activated by hyperpolarizing voltage steps. The adenosine action was theophylline- and pertussis toxin-sensitive indicating that the modulatory effect is mediated via an A1 receptor coupled to a G protein of the Gi or Go class.

2-Chloroadenosine↗
PubMed1989

The mesencephalic reticular formation as a link in the cortical control of exploratory and goal-directed behaviour.

The general accepted concept about the MRF as an unspecific ascending activating system concerns only one of its multiple functions. Investigations on more than 100 hooded rats of the Long-Evans strain with small bilateral symmetric lesions in dorsal, central and ventral subnuclei of the MRF brought out the following results pointing to further important functions: 1. Each lesion type produced a different syndrome of parameter changes of the spontaneous open field behavior with some common tendencies of reduced ambulatory and exploratory activities. 2. Visual placing responses were strongly reduced or totally abolished after lesions without tendencies of recovery. 3. Changes of locomotion and muscular tonus were quite different or even opposite in dorsal, central and ventral types of lesions. 4. In four tasks of postoperative active avoidance acquisition or retention and performance of preoperatively learned tasks the impairments were different related to the lesion type including a different loss in brightness discrimination. The results support the hypothesis that MRF subdivisions participate differently in information selection, tuning and coupling information with goal directed movements of different type. Lesions severely disturb the proper use of some information for a cue, especially visual cues when they are in the anterior part of the mesencephalon.

Animals↗
PubMed1989

[New non-invasive possibilities for assessing the function of the utero- and fetoplacental unit: Doppler sonography flow characteristics of selected arteries in normal pregnancy].

The introduction of the Doppler ultrasound measurements opened a new functional dimension in ultrasound diagnosis. For the first time, there is a possibility of estimating both the physiology and the pathophysiology of the uteroplacentofoetal haemodynamics with a noninvasive method during pregnancy. On the basis of more than 400 Doppler ultrasound vascular tests in uteroplacental arteries and in the umbilical artery of 110 pregnant women the blood flow velocity wave-forms were analyzed qualitatively with the pulsatility index, the resistance index and the S/D ratio. The gestational age-related decrease of these values in normal pregnancies reflects a reduction of the flow resistance in placental villous circulation. The values in retroplacentary arteries depend on the location of the tested vessel. The reference values are presented and the problems of the Doppler ultrasound numerical value inquiry and interpretation are discussed.

Arteries↗
PubMed1986

The effect of lesions in the mesencephalic reticular formation upon conditioned avoidance responses in rat. III. Lesions of the area subcuneiformis.

Two groups of 6 month old male hooded rats of the Long-Evans strain with bilateral symmetrical lesions in the anterior part of the mesencephalic area subcuneiformis (CUS) were compared with two sham-operated control groups (each group n = 8). CUS rats were absolutely unable to acquire a conditioned avoidance response (CAR) in a jump test; they even did not find out the escape possibility. Postoperative CAR acquisition of CUS rats in a horizontal alley was not different from controls, but their running speed was decreased (p less than 0.005). Lesioned rat's postoperative acquisition of brightness-discrimination was evidently disturbed and their error rate was still enhanced after 120 trials (p less than 0.005). Their reaction times of leaving the start box, however, were significantly lowered. The postoperative retention of preoperatively learnt CAR was very low. Relearning was possible in the Y-maze at lower level, but impossible in the jump test. The error rate decreased very slowly in the postoperative testing, whereas controls performed the brightness discrimination without errors as before. The unconditioned escape, however, was performed as correctly by CUS rats in the jump test as in the preoperative trials but rather slowly. The pattern of the behavioural syndrome after CUS lesions and the deficits in avoidance learning are possibly caused by a loss in sensory-motor coupling and a weakened ability to select visual, olfactory or painful stimuli which are important for the regulation of certain forms of behaviour.

Animals↗
PubMed1986

The pretectal region of the rat participates in the regulation of goal-directed behaviour.

Two groups of each 6 male hooded rats with bilateral symmetrical lesions in the anterior dorsolateral tegmentum including parts of the anterior and posterior pretectal nuclei and two sham-operated control groups were compared in different avoidance paradigms. The acquisition of conditioned avoidance responses (CAR) in a Y-maze was significantly retarded in lesioned rats and remained definitely on a lower performance level. Their reaction times (RTs) were significantly prolonged. Brightness discrimination was severely impaired. They had evidently troubles to correct their erroneous runs. After preoperative training lesioned rats had no retention deficit in the Y-maze performance, neither different RTs nor changes of running speed, but a deficit in brightness discrimination. Postoperative acquisition of CAR in a jump test was impossible. Retention of preoperatively learnt CAR in the jump test was zero, relearning was impossible reaching not more than 40% CAR performance after 8 sessions. The behavioural syndrome was different from other tegmental lesion types. Impaired brightness discrimination and vertical visual orientation are main symptoms of the more complex disturbance of goal-directed behaviour.

Animals↗
PubMed1984

The effect of lesions in the mesencephalic reticular formation upon conditioned avoidance responses in rat. II. Lesions of the area cuneiformis.

Hooded rats of the Long-Evans strain were not able to acquire a conditioned avoidance response (CAR) in a jump test when they were injured by bilateral symmetric lesions in the area cuneiformis (CU) of the mesencephalic reticular formation. The acquisition of a simple CAR in a Y-maze was not impaired irrespective of the size of the lesion. However, lesioned rats ran significantly slowlier to the maze exit in simple and discrimination tasks and displayed more erroneous runs in dark-light discrimination sessions. These deficits were not observed when rats with small lesions in the anterior CU (CU-1 group) had preoperatively learnt the dark-light discrimination, but they were observed when preoperatively trained rats were injured by caudally extended lesions (CU-2 group). After preoperative training CU-1 rats had a great retention deficit in the jump test compared with no deficit in a sham-operated group. They were unable to relearn the task, whereas rats with dorsally extended lesions including the nucleus commissurae posterioris (NCP-CU group) had less deficit and relearnt the CAR in the jump test. Animals of this group performed an enhanced number of intertrial responses and showed increased arrest reactions with goal-directed attention evoked by the conditioned stimulus. The results indicate - together with the observed behavioural syndrome of disturbed locomotion, reduced orienting responses and exploratory behaviour - that the CU is an important structure for the integration of goal-directed behaviour.

Animals↗
PubMed1984

The effect of lesions in the mesencephalic reticular formation upon conditioned avoidance responses in rat: I. Lesions of the nucleus commissurae posterioris.

After bilateral symmetric lesions of the n. commissurae posterioris (NCP) hooded rats of the Long-Evans strain did not acquire the conditioned avoidance response (CAR) in a jumping test. The NCP rats were rather unable to find out the escape possibility on the rod hanging in the middle of the apparatus. They did not learn the context between the conditioned stimulus (CS), the unconditioned stimulus (UCS) and the jump. In an Y-maze formation of CAR was even better in NCP rats than in sham-operated controls because of their shorter reaction times and their higher running speed. Their brightness discrimination, on the other hand, was significantly impaired and erroneous runs were only reduced to a low insignificant amount after more than 100 trials. Lesions in the NCP had no severe effects upon preoperatively learnt CARs, but brightness discrimination was still impaired. From these results it may be concluded that NCP plays a role in the formation of goal-directed behaviour depending on external cues and in actual visually guided behaviour.

Animals↗
PubMed1983

Open field behaviour of rats after various mesencephalic lesions.

Hooded rats of the Long-Evans strain with small bilateral symmetric lesions of the pretectum (PR, n = 10), the nucleus commissurae posterioris (NCP, n = 14), area cuneiformis (CU, n = 10), area subcuneiformis (CUS, n = 11) and with combined lesions of CU and NCP (n = 6) were compared in an open field (OF) situation with sham-operated controls (C, n = 8). All lesioned rats showed significantly decreased crossing of 15 cm squares in the OF, which were controlled by infra-red beams. This decrease was stronger after dorsal lesions (55% of controls) than after ventral ones (80% of controls). In all lesioned groups with exception of CUS rats the duration of immobility was significantly prolonged, maximally after NCP lesions (980%). When NCP rats moved, they had a higher rate of crossings per second (150%) whereas CUS rats moved more slowly (71% crossings per second related to controls). The stay on peripheral fields was prolonged in PR rats and reduced in NCP rats. The number of rearings in all lesioned animals was less than 25% of control values. This was closely correlated with a strong reduction of climbings at the walls except after PR lesions. The third parameter of exploratory behaviour - the duration of sniffing - was significantly diminished except in CUS rats, in which sniffing was significantly enhanced compared with controls. Lesioned rats had shorter grooming latencies with a minimum in CUS rats (23% of controls) and prolonged grooming durations with a maximum in NCP-CU rats (267%). The results demonstrate that relatively small lesions in the anterior mesencephalic reticular formation (MRF) lead to remarkable changes in the spontaneous behaviour of rats with widely differing patterns of behavioural parameters depending on the locus of bilateral symmetric lesions. The data suggest in contrast to the hypothesis of an unspecific modulating function of the MRF, that their different parts play a specific role in the integration of various behavioural patterns.

Animals↗
PubMed1977

Transformation of normal hamster cells by benzo(a)pyrene diol-epoxide.

The frequency of cell transformation was determined after treatment of normal hamster embryo cells with benzo(a)pyrene (BP) and six of its metabolites. These metabolites included the trans 4,5-, 7,8- and 9,10-dihydrodiols; the 4,5-epoxide; and two stereoisomers of the non-K-region diol epoxides r-7, t-8-dihydroxy t-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 1) and r-7, t-8, dihydroxy c-9, 10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene (diol-epoxide 11). The trans 7,8-dihydrodiol was more active than the other two dihydrodiols tested and was also more active than the parent hydrocrabon BP. Of the three epoxides tested, the diol-epoxide 1 was more active than the 4,5-epoxide and diol-epoxide 11. The results suggest that diol-epoxide 1 is a major cell-transforming metabolite of BP.

Animals↗