Search PubMed⌕ Search

Biomedical subjects

P Jonas

Publications and source records attributed to P Jonas.

At least 55 records · Page 3Linked to original sources

Differences in Ca2+ permeability of AMPA-type glutamate receptor channels in neocortical neurons caused by differential GluR-B subunit expression.

Fast excitatory synaptic transmission in the CNS is mediated by AMPA-type glutamate receptor (GluR) channels. Heterologous expression suggested that the Ca2+ permeability of these receptors critically depends on the subunit composition. Using patch-clamp techniques in brain slices, we found that the Ca2+ permeability of native AMPA-type GluRs was markedly higher in nonpyramidal (PCa/PK approximately 0.63) than in pyramidal (PCa/PK approximately 0.05) neurons of rat neocortex. Analysis of mRNA in single cells indicated that the relative abundance of GluR-B-specific mRNA was significantly lower in nonpyramidal (GluR-B/GluR-non-B approximately 0.3) than in pyramidal (GluR-B/GluR-non-B approximately 3) cells. This suggests that differences in relative abundance of GluR-B-specific mRNA generate functional diversity of AMPA-type GluRs in neurons with respect to Ca2+ permeability.

Animals↗

Mechanisms shaping glutamate-mediated excitatory postsynaptic currents in the CNS.

Excitatory postsynaptic currents in neurones of the central nervous system have a dual-component time course that results from the co-activation of AMPA/kainate-type and NMDA-type glutamate receptors. New approaches in electrophysiology and molecular biology have provided a better understanding of the factors that determine the kinetics of excitatory postsynaptic currents. Recent studies suggest that the time course of neurotransmitter concentration in the synaptic cleft, the gating properties of the native channels, and the glutamate receptor subunit composition all appear to be important factors.

Animals↗

Quantal analysis of excitatory postsynaptic currents at the hippocampal mossy fiber-CA3 pyramidal cell synapse.

Unitary excitatory postsynaptic current (EPSC) amplitude histograms obtained from synapses between mossy fibers (MF) and CA3 pyramidal cells in hippocampus were analyzed with the aim of deriving the mean peak current of quantal events, its coefficient of variation CVq, the number of release sites NS, and the release probability PR. Unitary EPSC histograms with multiple peaks were fitted satisfactorily under the assumption that quantal events have a slightly skewed amplitude distribution and that the release mechanism is described by models with either binomial (standard), nonuniform, or nonstationary statistics. The average peak current of the quantal event derived from these fits reflected the opening of between 15 and 65 glutamate receptor (GluR) channels of the AMPAR subtype. The variability in the amplitude of quantal events is characterized by a CVq of 25% to 30%. The best fits to multiple peak EPSC histograms are obtained if it is assumed that the number of release sites contained within a single MF-bouton is between 8 and 21, a value comparable to the published number of morphologically measured presynpatic active zones and postsynaptic densities (PSDs) of individual MF-CA3 synapses. This suggests that at the MF-CA3 synapse each presynaptic zone and its associated PSD act as independent units, contributing one quantal event to unitary EPSCs. Simulations of unitary EPSC distributions, based on measurements of PSD size could, however, indicate that the interpretation of multipeak EPSC amplitude distributions at MF-CA3 synapses in terms of fluctuating release probabilities might be an over-simplification, and that postsynaptic factors may contribute significantly to fluctuations of unitary EPSC amplitudes.

Animals↗

Ureteropelvic junction obstruction: relation of etiology and age at surgical repair to clinical outcome.

Ureteropelvic junction (UPJ) obstruction is a congenital anomaly either caused by intrinsic narrowing of the upper ureter or by extrinsic pressure on the ureter caused by aberrant vessels or fibrous bands. We reviewed 121 cases of pyeloplasties performed in our department for UPJ obstruction. The cases were grouped by age and by the underlying pathology. Postoperative urographic evaluation showed that dismembered pyeloplasty was successful in 98.4% of the patients, with no significant difference between age groups. Persistence or recurrence of preoperative symptoms occurred in some patients (16.6%). Extrinsic obstruction of the ureter was associated with better postoperative clinical results and less recurrence of symptoms.

Adolescent↗

Detailed passive cable models of whole-cell recorded CA3 pyramidal neurons in rat hippocampal slices.

Tight-seal whole-cell recordings were made from cleaned somata of CA3 pyramidal cells deep in hippocampal slices from 19-21-d-old rats. The cells were filled with biocytin, and their voltage responses to short current pulses were recorded. After washout of initial sag, responses scaled linearly with injected current and were stable over time. The dendritic and axonal arbors of four cells were reconstructed and measured using light microscopy. Dendritic spines and axonal boutons were counted and the additional membrane area was incorporated into the relevant segments. The morphology of each neuron was converted into a detailed branching cable model by assuming values for specific membrane capacitance Cm and resistance Rm, and cytoplasmic resistivity Ri. These parameters were optimized for each cell by directly matching the model's response to that of the real cell by means of a modified weighted least-squares fitting procedure. By comparing the deviations between model and experimental responses to control noise recordings, approximate 95% confidence intervals were established for each parameter. If a somatic shunt was allowed, a wide range of possible Rm values produced acceptable fits. With zero shunt, Cm was 0.7-0.8 microFcm-2, Ri was 170-340 omega cm, and Rm ranged between 120 and 200 k omega cm2. The electrotonic lengths of the basal and oblique dendrites were 0.2-0.3 space constants, and those of the apical tufts were 0.4-0.7 space constants. The steady-state electrical geometry of these cells was therefore compact; average dendritic tip/soma relative synaptic efficacies were > 93% for the basal and oblique dendrites, and > 81% for the tufts. With fast transient synaptic inputs, however, the models produced a wide range of postsynaptic potential shapes and marked filtering of voltage-clamp currents.

Animals↗

AMPA-type glutamate receptors--nonselective cation channels mediating fast excitatory transmission in the CNS.

In recent years, considerable progress in our understanding of the molecular events underlying excitatory synaptic transmission has been made. This progress was mainly achieved by technical advances, among them the patch-clamp technique in brain slices (Edwards et al., 1989), fast application of agonists (Franke et al., 1987), and cloning and functional expression of GluR channels of the nonNMDA type (e.g., Hollmann et al., 1989). A suitable model for studying excitatory postsynaptic currents (EPSCs) in the brain slice with patch-clamp techniques is the mossy fiber synapse on CA3 pyramidal cells of rat hippocampus (MF-CA3 synapse). This synapse is located close to the cell soma and should provide almost ideal space-clamp conditions. A comparison of MF-CA3 EPSCs with the currents activated by fast application of glutamate on membrane patches isolated from CA3 cell somata suggests that the concentration of glutamate in the synaptic cleft during excitatory synaptic transmission is high (about 1 mM) and that the transmitter remains in the synaptic cleft only briefly (about 1 ms). It seems likely that desensitization influences the peak amplitude of the EPSC in several ways. Brief pulses of glutamate cause desensitization, from which the glutamate receptor channels recover only slowly, and micromolar ambient glutamate concentrations produce desensitization at equilibrium. From the functional properties of recombinant GluR channels, in situ hybridization data, and patch-clamp experiments on different neuronal and nonneuronal cell types, a picture of the molecular identity of native channels emerges. In neurons of the hippocampus the pharmacological features of these channels were similar to recombinant channels assembled from subunits of the AMPA/kainate subtype which are strongly expressed in these cells. The native channels are characterized by outward rectification of the steady-state I-V and low Ca permeability, similar to recombinant channels containing the GluR-B subunit. This is consistent with the ubiquitous expression of this subunit in hippocampal neurones. In contrast, GluR channels from cerebellar glial cells, which uniquely in the central nervous system lack the expression of GluR-B subunits, show double rectification and high Ca permeability. The results suggest that the native functional nonNMDA glutamate receptor channels in the CNS are assembled form subunits of the AMPA/kainate subtype in a cell-specific way, with the functional properties of GluR channels in neurones being dominated by the GluR-B subunit.

Animals↗

Quantal components of unitary EPSCs at the mossy fibre synapse on CA3 pyramidal cells of rat hippocampus.

1. Excitatory postsynaptic currents (EPSCs) were recorded in CA3 pyramidal cells of hippocampal slices of 15- to 24-day-old rats (22 degrees C) using the whole-cell configuration of the patch clamp technique. 2. Composite EPSCs were evoked by extracellular stimulation of the mossy fibre tract. Using the selective blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonopentanoic acid (APV), a major alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/kainate receptor-mediated component and a minor NMDA receptor-mediated component with slower time course were distinguished. For the AMPA/kainate receptor-mediated component, the peak current-voltage (I-V) relation was linear, with a reversal potential close to 0 mV. The half-maximal blocking concentration of CNQX was 353 nM. 3. Unitary EPSCs of the mossy fibre terminal (MF)-CA3 pyramidal cell synapse were evoked at membrane potentials of -70 to -90 mV by low-intensity extracellular stimulation of granule cell somata using fine-tipped pipettes. The EPSC peak amplitude as a function of stimulus intensity showed all-or-none behaviour. The region of low threshold was restricted to a few micrometres. This suggests that extracellular stimulation was focal, and that the stimulus-evoked EPSCs were unitary. 4. Latency and rise time histograms of EPSCs evoked by granule cell stimulation showed narrow unimodal distributions within each experiment. The mean latency was 4.2 +/- 1.0 ms, and the mean 20-80% rise time was 0.6 +/- 0.1 ms (23 cells). When fitted within the range 0.7 ms to 20 ms after the peak, the decay of the EPSCs with the fastest rise (rise time 0.5 ms or less) could be described by a single exponential function; the mean time constant was in the range 3.0-6.6 ms with a mean of 4.8 ms (8 cells). 5. Peak amplitudes of the EPSCs evoked by suprathreshold granule cell stimulation fluctuated between trials. The apparent EPSC peak conductance in normal extracellular solution (2 mM Ca2+, 1 mM Mg2+), excluding failures, was 1 nS. Reducing the Ca2+ concentration and increasing the Mg2+ concentration reduced the mean peak amplitude in a concentration-dependent manner. 6. Peaks in EPSC peak amplitude distributions were apparent in low Ca2+ and high Mg2+. Using the criteria of equidistance and the presence of peaks and dips in the autocorrelation function, five of nine EPSC peak amplitude distributions were judged to be quantal.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗

Hematuria and voiding disorders in children caused by congenital urethral polyps. Principles of diagnosis and management.

Congenital urethral polyps may cause hematuria, various degrees of outflow obstruction and display a variety of, mostly nonspecific micturition abnormalities in young boys and infants, and should be considered and investigated when recurrent or persistent hematuria and voiding disturbances are encountered. Voiding cystography is the best available diagnostic method to detect urethral polyps. Following diagnosis, prompt complete resection of polyp is indicated. Resolution of signs and symptoms and excellent prognosis are the rule in most of the reported cases. In view of the rarity of this significant pathological condition, we present our experience with 6 children who suffered from urethral polyps and outline the principles of diagnostic evaluation and management of the child with urethral polyp.

Child, Preschool↗

[Endometriosis of the bladder].

We report a case of endometriosis of the bladder in a 32-year-old healthy woman suffering from longstanding suprapubic pain, and urinary urgency and frequency. The disease, which is uncommon, usually has a high morbidity rate and is difficult to diagnose. A high level of suspicion is necessary for diagnosis, since neither the clinical presentation, nor imaging procedures are pathognomonic for endometriosis.

Adult↗

Calcium-permeable AMPA-kainate receptors in fusiform cerebellar glial cells.

Glutamate-operated ion channels (GluR channels) of the L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate subtype are found in both neurons and glial cells of the central nervous system. These channels are assembled from the GluR-A, -B, -C, and -D subunits; channels containing a GluR-B subunit show an outwardly rectifying current-voltage relation and low calcium permeability, whereas channels lacking the GluR-B subunit are characterized by a doubly rectifying current-voltage relation and high calcium permeability. Most cell types in the central nervous system coexpress several subunits, including GluR-B. However, Bergmann glia in rat cerebellum do not express GluR-B subunit genes. In a subset of cultured cerebellar glial cells, likely derived from Bergmann glial cells. GluR channels exhibit doubly rectifying current-voltage relations and high calcium permeability, whereas GluR channels of cerebellar neurons have low calcium permeability. Thus, differential expression of the GluR-B subunit gene in neurons and glia is one mechanism by which functional properties of native GluR channels are regulated.

Animals↗

A TEA-insensitive flickering potassium channel active around the resting potential in myelinated nerve.

A novel potassium-selective channel which is active at membrane potentials between -100 mV and +40 mV has been identified in peripheral myelinated axons of Xenopus laevis using the patch-clamp technique. At negative potentials with 105 mM-K on both sides of the membrane, the channel at 1 kHz resolution showed a series of brief openings and closings interrupted by longer closings, resulting in a flickery bursting activity. Measurements with resolution up to 10 kHz revealed a single-channel conductance of 49 pS with 105 mM-K and 17 pS with 2.5 mM-K on the outer side of the membrane. The channel was selective for K ions over Na ions (PNa/PK = 0.033). The probability of being within a burst in outside-out patches varied from patch to patch (> 0.2, but often > 0.9), and was independent of membrane potential. Open-time histograms were satisfactorily described with a single exponential (tau o = 0.09 msec), closed times with the sum of three exponentials (tau c = 0.13, 5.9, and 36.6 msec). Sensitivity to external tetraethylammonium was comparatively low (IC50 = 19.0 mM). External Cs ions reduced the apparent unitary conductance for inward currents at Em = -90 mV (IC50 = 1.1 mM). Ba and, more potently, Zn ions lowered not only the apparent single-channel conductance but also open probability. The local anesthetic bupivacaine with high potency reduced probability of being within a burst (IC50 = 165 nM). The flickering K channel is clearly different from the other five types of K channels identified so far in the same preparation. We suggest that this channel may form the molecular basis of the resting potential in vertebrate myelinated axons.

Animals↗

Ectopic ureterocele in adults with a comparison of the anomaly in children.

Ectopic ureteroceles, while not uncommon in children, have been reported only rarely in adults. We present five adults with ectopic ureteroceles with emphasis on the varied clinical and radiographic manifestations. These findings were compared with those in 32 children with ectopic ureterocele. It was found that the clinical presentation differed in adults and children, but the radiological findings were similar. The diagnosis was in some cases delayed for many years. The anomaly could not be detected by imaging means in two of five adults and eight of 32 children, and was found only at surgery.

Adult↗

Diverticula of the male urethra: a review of 61 cases.

Sixty-one cases of diverticulum of the male urethra were reviewed. This group included 10 patients with congenital and 51 with acquired diverticula. The etiology of the acquired variety, the radiological findings, and the frequency of appearance in both congenital and acquired diverticula of the urethra during a 30-year period are described.

Adolescent↗

Circumcision in hemophilia: the use of fibrin glue for local hemostasis.

Circumcision can be fatal in hemophilia patients unless they are treated with the missing coagulation factor. We describe 10 severe hemophilia patients in whom circumcision was performed with local fibrin glue instead of infusion of factor concentrate. Of the 10 patients 3 had postoperative bleeding and only 2 of them required infusion of factor VIII concentrate. Fibrin glue is a useful treatment modality for circumcision in patients with bleeding diathesis, and it is safer and cheaper than the infusion of factor concentrate.

Adolescent↗

A 20-year experience with treatment of ectopic ureteroceles.

Between 1970 and 1990 a total of 37 patients (female-to-male ratio 3.6:1) was diagnosed and treated at our institution for ectopic ureterocele. Urinary tract infection was the most frequent mode of presentation (59%). Of the patients 54% were less than 3 years old at operation. Transurethral incision of ectopic ureterocele served only as a decompressive procedure for acutely ill infants and was followed with a high incidence (80%) of resultant vesicoureteral reflux. The elective surgical policy was individualized based on renal function and presence of vesicoureteral reflux. Overall results within the various groups were generally satisfactory regarding eradication of urinary tract infections, preservation of renal function and continence or treatment of vesicoureteral reflux. Upper pole heminephrectomy and partial ureterectomy were performed in 14 patients with 3 (21%) requiring reoperation, including only 2 (14%) subsequent reimplantations. Thus, we believe that an expectant approach to the lower urinary tract is well recommended in the majority of the patients with a poorly functioning ipsilateral renal segment. A modified technique of total reconstruction, performing only partial ureterectomy with double barrel reimplantation, was successful in 7 patients.

Child↗

Low loop cutaneous ureterostomy and subsequent reconstruction: 20 years of experience.

Between 1970 and 1990 we constructed low loop cutaneous ureterostomies in 50 patients with grossly dilated collecting systems. Patient age ranged from 6 days to 3 years. The indication for all urinary diversions was an anomaly of the lower urinary tract associated with marked ureteral dilatation considered to require decompression because of either urinary tract infections or renal functional impairment. Clinical and radiological followup was maintained between establishment of the cutaneous ureterostomy and complete reconstruction, and revealed marked improvement indistinguishable from that obtained by high diversions. Undiversion was performed after 3 to 69 months, usually simultaneously with definitive correction of the underlying anomaly. The main advantage of our presented technique is the opportunity to resect the distal ureteral limb and to perform simple ureteroneocystostomy using the proximal limb. Besides its technical simplicity, this technique obviates possible complications that may be attributed to ureteral anastomosis and compromised blood supply, thus, it is well recommended.

Child, Preschool↗