CK2 accumulation at the axon initial segment depends on sodium channel Nav1.

Accumulation of voltage-gated sodium channel Nav1 at the axon initial segment (AIS), results from a direct interaction with ankyrin G. This interaction is regulated in vitro by the protein kinase CK2, which is also highly enriched at the AIS. Here, using phosphospecific antibodies and inhibition/depletion approaches, we showed that Nav1 channels are phosphorylated in vivo in their ankyrin-binding motif. Moreover, we observed that CK2 accumulation at the AIS depends on expression of Nav1 channels, with which CK2 forms tight complexes. Thus, the CK2-Nav1 interaction is likely to initiate an important regulatory mechanism to finely control Nav1 phosphorylation and, consequently, neuronal excitability.

Altered expression and localization of hippocampal A-type potassium channel subunits in the pilocarpine-induced model of temporal lobe epilepsy.

Altered ion channel expression and/or function may contribute to the development of certain human epilepsies. In rats, systemic administration of pilocarpine induces a model of human temporal lobe epilepsy, wherein a brief period of status epilepticus (SE) triggers development of spontaneous recurrent seizures that appear after a latency of 2-3 weeks. Here we investigate changes in expression of A-type voltage-gated potassium (Kv) channels, which control neuronal excitability and regulate action potential propagation and neurotransmitter release, in the pilocarpine model of epilepsy. Using immunohistochemistry, we examined the expression of component subunits of somatodendritic (Kv4.2, Kv4.3, KChIPl and KChIP2) and axonal (Kv1.4) A-type Kv channels in hippocampi of pilocarpine-treated rats that entered SE. We found that Kv4.2, Kv4.3 and KChIP2 staining in the molecular layer of the dentate gyrus changes from being uniformly distributed across the molecular layer to concentrated in just the outer two-thirds. We also observed a loss of KChIP1 immunoreactive interneurons, and a reduction of Kv4.2 and KChIP2 staining in stratum radiatum of CA1. These changes begin to appear 1 week after pilocarpine treatment and persist or are enhanced at 4 and 12 weeks. As such, these changes in Kv channel distribution parallel the acquisition of recurrent spontaneous seizures as observed in this model. We also found temporal changes in Kv1.4 immunoreactivity matching those in Timm's stain, being expanded in stratum lucidum of CA3 and in the inner third of the dentate molecular layer. Among pilocarpine-treated rats, changes were only observed in those that entered SE. These changes in A-type Kv channel expression may contribute to hyperexcitability of dendrites in the associated hippocampal circuits as observed in previous studies of the effects of pilocarpine-induced SE.

Dendritic A-type potassium channel subunit expression in CA1 hippocampal interneurons.

Voltage-gated potassium (Kv) channels are important and diverse determinants of neuronal excitability and exhibit specific expression patterns throughout the brain. Among Kv channels, Kv4 channels are major determinants of somatodendritic A-type current and are essential in controlling the amplitude of backpropagating action potentials (BAPs) into neuronal dendrites. BAPs have been well studied in a variety of neurons, and have been recently described in hippocampal and cortical interneurons, a heterogeneous population of GABAergic inhibitory cells that regulate activity of principal cells and neuronal networks. We used well-characterized mouse monoclonal antibodies against the Kv4.3 and potassium channel interacting protein (KChIP) 1 subunits of A-type Kv channels, and antibodies against different interneuron markers in single- and double-label immunohistochemistry experiments to analyze the expression patterns of Kv4.3 and KChIP1 in hippocampal Ammon's horn (CA1) neurons. Immunohistochemistry was performed on 40 mum rat brain sections using nickel-enhanced diaminobenzidine staining or multiple-label immunofluorescence. Our results show that Kv4.3 and KChIP1 component subunits of A-type channels are co-localized in the soma and dendrites of a large number of GABAergic hippocampal interneurons. These subunits co-localize extensively but not completely with markers defining the four major interneuron subpopulations tested (parvalbumin, calbindin, calretinin, and somatostatin). These results suggest that CA1 hippocampal interneurons can be divided in two groups according to the expression of Kv4.3/KChIP1 channel subunits. Antibodies against Kv4.3 and KChIP1 represent an important new tool for identifying a subpopulation of hippocampal interneurons with a unique dendritic A-type channel complement and ability to control BAPs.

Eogenetic karst hydrology: insights from the 2004 hurricanes, peninsular Florida.

Eogenetic karst lies geographically and temporally close to the depositional environment of limestone in warm marine water at low latitude, in areas marked by midafternoon thunderstorms during a summer rainy season. Spring hydrographs from such an environment in north-central Florida are characterized by smooth, months-long, seasonal maxima. The passage of Hurricanes Frances and Jeanne in September 2004 over three field locations shows how the eogenetic karst of the Upper Floridan Aquifer responds to unequivocal recharge events. Hydrographs at wells in the High Springs area, Rainbow Springs, and at Morris, Briar, and Bat Caves all responded promptly with a similar drawn-out rise to a maximum that extended long into the winter dry season. The timing indicates that the typical hydrograph of eogenetic karst is not the short-term fluctuations of springs in epigenic, telogenetic karst, or the smoothed response to all the summer thunderstorms, but rather the protracted response of the system to rainfall that exceeds a threshold. The similarity of cave and noncave hydrographs indicates distributed autogenic recharge and a free communication between secondary porosity and permeable matrix-both of which differ from the hydrology of epigenic, telogenetic karst. At Briar Cave, drip rates lagged behind the water table rise, suggesting that recharge was delivered by fractures, which control the cave's morphology. At High Springs, hydrographs at the Santa Fe River and a submerged conduit apparently connected to it show sharp maxima after the storms, unlike the other cave hydrographs. Our interpretation is that the caves, in general, are discontinuous.

Springflow hydrographs: eogenetic vs. telogenetic karst.

Matrix permeability in the range of 10(-11) to 10(-14) m(2) characterizes eogenetic karst, where limestones have not been deeply buried. In contrast, limestones of postburial, telogenetic karst have matrix permeabilities on the order of 10(-15) to 10(-20) m(2). Is this difference in matrix permeability paralleled by a difference in the behavior of springs draining eogenetic and telogenetic karst? Log Q/Q(min) flow duration curves from 11 eogenetic-karst springs in Florida and 12 telogenetic-karst springs in Missouri, Kentucky, and Switzerland, plot in different fields because of the disparate slopes of the curves. The substantially lower flow variability in eogenetic-karst springs, which results in the steeper slopes of their flow duration curves, also makes for a strong contrast in patterns (e.g., "flashiness") between the eogenetic-karst and telogenetic-karst spring hydrographs. With respect to both spring hydrographs and the flow duration curves derived from them, the eogenetic-karst springs of Florida are more like basalt springs of Idaho than the telogenetic-karst springs of the study. From time-series analyses on discharge records for 31 springs and published time-series results for 28 additional sites spanning 11 countries, we conclude that (1) the ratio of maximum to mean (Q(max)/Q(mean)) discharge is less in springs of eogenetic karst than springs of telogenetic karst; (2) aquifer inertia (system memory) is larger in eogenetic karst; (3) eogenetic-karst aquifers take longer to respond to input signals; and (4) high-frequency events affect discharge less in eogenetic karst. All four of these results are consistent with the hypothesis that accessible storage is larger in eogenetic-karst aquifers than in telogenetic-karst aquifers.

Metaphors and models: the ASR bubble in the Floridan aquifer.

Studies at the intersection of cognitive science and linguistics have revealed the crucial role that metaphors play in shaping our thoughts about phenomena we cannot see. According to the domains interaction theory of cognition, a metaphoric expression sets up mappings between a target domain that we wish to understand and a familiar source domain. The source domain contains elements ("commonplaces") that we manipulate mentally, like parts of an analogue model, to illuminate the target domain. This paper applies the structure of domains interaction theory to analyze the dynamics of a metaphor in hydrogeology: the so-called bubble formed by water injected into an aquifer during aquifer storage and recovery (ASR). Of the four commonplaces of bubbles--(1) they are discrete; (2) they are geometrically simple; (3) they rise; and (4) they burst--we focus on the first two using both displacement and dispersion (tracer) models for both homogeneous and heterogeneous storage zones patterned from geological studies of the Suwannee Limestone of Sarasota County, Florida. The displacement model easily shows that "bottle brush" better represents the geometric complexity predicted from the known and inferred heterogeneity. There is virtually no difference, however, in the prediction of recovery efficiency using the dispersion model for a bubble (homogeneous flow zone) vs. bottle brush (heterogeneous flow zone). On the other hand, only the bottle brush reveals that unrecovered tracer is located preferentially in the low-permeability layers that lie adjacent to high-permeability channels in the flow zones.

Small conductance calcium-activated K+ channels, SkCa, but not voltage-gated K+ (Kv) channels, are implicated in the antinociception induced by CGS21680, a A2A adenosine receptor agonist.

It has been shown that A2A adenosine receptors are implicated in pain modulation. The precise mechanism by which activation of A2A receptors produces analgesic effects, however, remains unclear. The aim of this study was to investigate the possible involvement of apamin-sensitive calcium-activated potassium channels (SKCa) and voltage-gated potassium (Kv) channels in A2A receptor activation-induced analgesic effects. Using mice, we evaluated the influence of apamin, a non specific blocker of SKCa channels, Lei-Dab7 (an analog of scorpion Leiurotoxin), a selective blocker of SKCa2 channels, and kaliotoxin (KTX) a Kv channel blocker, on the CGS 21680 (A2A adenosine receptor agonist)-induced increases in hot plate and tail pinch latencies. All drugs were injected in mice via the intracerebroventricular route. We found that apamin and Lei-Dab7, but not KTX, reduced antinociception produced by CGS21680 on the hot plate and tail pinch tests in a dose dependent manner. Lei-Dab 7 was more potent than apamin in this regard. We conclude that SKCa but not Kv channels are implicated in CGS 21680-induced antinociception.

Use of fusion protein constructs to generate potent immunotherapy and protection against scorpion toxins.

We report the use of recombinant scorpion toxins in the form of fusion proteins as antigens for immunisation in rabbits and mice: the aim was to produce in these animal models protective antisera against the most lethal alpha-type toxins in the venom from the North African scorpion Androctonus australis. The cDNAs encoding AaH I, AaH II and AaH III (the three major alpha-type toxins acting on voltage-sensitive sodium channels) were fused to the sequence encoding the maltose binding protein (MBP). The constructs (MBP-AaH I, MBP-AaH II, MBP-AaH I+II and MBP-AaH III) were expressed in Escherichia coli, and resulting fusion proteins were translocated to the periplasmic space. The recombinant fusion proteins were characterised and used as antigens to generate antibodies in rabbits. These antibodies raised specifically recognised their corresponding radiolabelled-toxin with affinities in the 0.1nM range. In vitro neutralisation assays indicated that 1ml of serum raised against a mixture of fusion proteins was able to neutralise 15 LD(50) of the toxic fraction (AaH-G50) purified from the crude venom by molecular filtration through Sephadex G50. In vivo, the fusion proteins induced a long-term protection in mice against the lethal effects of AaH-G50 or of the native toxins. Ten weeks after the beginning of the immunisation programme, mice were challenged with various toxins or AaH-G50 doses. Mice were fully protected against three LD(50) of AaH-G50. Our work shows that fusion protein constructs can be used as a vaccine providing efficient immune protection against A. australis venom.

A new class of scorpion toxin binding sites related to an A-type K+ channel: pharmacological characterization and localization in rat brain.

A new scorpion toxin (3751.8 Da) was isolated from the Buthus martensi venom, sequenced and chemically synthesized (sBmTX3). The A-type current of striatum neurons in culture completely disappeared when 1 microM sBmTX3 was applied (Kd=54 nM), whereas the sustained K+ current was unaffected. 125I-sBmTX3 specifically bound to rat brain synaptosomes (maximum binding=14 fmol x mg(-1) of protein, Kd=0.21 nM). A panel of toxins yet described as specific ligands for K+ channels were unable to compete with 125I-sBmTX3. A high density of 125I-sBmTX3 binding sites was found in the striatum, hippocampus, superior colliculus, and cerebellum in the adult rat brain.

Where is imaging going in rheumatology?

Four new approaches to imaging are now becoming available. First is filmless radiology, with flat detectors that 'permit access' to PACS, the picture archiving communication system, and teleteaching. Second is ultrasonography (US), involving three-dimensional volume, harmonic Doppler energy and digital technology techniques, with contrast agents and biopsy needles. Next is computer tomography (CT), using volume acquisition multislices, spiral reconstruction and solid detectors, as well as multidetectors. Finally comes magnetic resonance imaging (MRI). A low magnetic field with an open MRI scan permits interventional radiology in musculoskeletal disease. High magnetic fields are mainly used for clinical research and permit rapid examination, in approximately 10 minutes. In interventional radiology, many procedures can be performed with the guidance of digital radiography, US or MRI. Two areas of localization have to be considered: the spine and the peripheral joints, particularly the shoulder, wrist and foot. Guidelines contribute to good medical practice, but there are other considerations, such as machine accessibility, the nature of the treatment, the personality of the patient and the role of the hospital. Overinvestigation has to be avoided for four reasons: an increase in patient anxiety, the cost of health-care management, the risk of irradiation and sometimes the lack of diagnostic value of these procedures. In rheumatoid arthritis, MRI can detect lesions at an earlier stage of their development and identify subtle lesions and synovitis. Imaging (using x-rays, MRI and US) is important in the assessment of the effectiveness of slow-acting drugs in rheumatoid arthritis, especially since joint damage can progress in spite of a clinical improvement in joint inflammation. In the future, teletransmission, by the Internet or intranet and using PACS, will change our approach to the diagnosis of musculoskeletal disease. Future developments therefore include PACS, filmless radiology, the Internet and intranet, harmonic US, multidetector CT scanning and open MRI on the technical side, as well as the study of cartilage and international radiology on the clinical side.

Ulnar nerve compression at the wrist by a synovial cyst successfully treated with percutaneous puncture and corticosteroid injection.

A case of ulnar nerve palsy due to a conduction block in the deep motor branch at the wrist is reported. The cause was a rapidly growing synovial cyst. Ultrasonography and computed tomography were performed to determine the exact location of the cyst, which was punctured and injected with corticosteroid. Function promptly returned to normal after this procedure.

[Hyaloretinal degeneration with osteoporosis and bone fragility. Pseudoglioma with bone fragility (author's transl)]. / Dénénérescence hyalido-rétinienne avec ostéoporose et fragilité osseuse. Psesudo-gliome avec fragilité osseuse.

Three patients from the same family presented hyaloretinal dysplasia (pseudoglioma) associated with osteoporosis and bone fragility. Results of clinical, ophthalmological, and radiological examinations in these three cases are described, together with those reported in the literature concerning 21 other cases of this rare autosomal-recessive affection.

[Clinical, radiological and pathological study of Ewing's sarcoma of the lumbar spine. Round cell sarcomas. Report on three cases (author's transl)]. / Etude anatomo-radio-clinique des sarcomes d'Ewing du rachis lombaire. Sarcomes à cellules rondes. A propos de trois cas.

Two cases of primary bone condensation type Ewing's sarcoma of a lumbar vertebra are described in children aged 8 and 10 years, as well as one case of the osteolytic form in a 14-year-old child. Ewing's sarcoma very rarely occurs in the spine, and the type with bone condensation is almost exclusively of a primary nature. The tumour extends simultaneously into the epidural space and the perispinal planes. Intravenous urography and myelography with metrizamide are therefore essential for evaluating the degree of tumour extension. Computed tomography examinations are also now necessary. Prognosis is bad and current therapeutic possibilities limited. Histological diagnosis is the only means of distinguishing Ewing's sarcoma from other round cell sarcomas in or around the spine.

Cauda equina syndrome complicating ankylosing spondylitis: use of electromyography and computerised tomography in diagnosis.

A case of the cauda equina syndrome complicating ankylosing spondylitis (AS) is described. An unusual feature of this case was the relapsing and remitting nature of the condition, but there is sufficient evidence to explain the clinical picture on the basis of a recurrent intraspinal inflammatory process. The clinical and radiological features are similar to those of a further 28 reported in the literature. An electromyogram (EMG) proved important in defining the extent of neurological involvement. Computerised tomography (CT) showed marked laminar erosion and no bony exit foramen encroachment. We believe that the clinical diagnosis of this condition can be adequately confirmed with plain radiology, EMG, and CT scan.

Calcifications of the hip in infants and children. New cases and long-term follow-up.

10 cases of calcification of the peripheral cartilaginous contour of the femoral head in infants are reported. In 7 cases calcification were discovered by chance at a radiological examination done for another purpose. In 3 cases the examination was done for limp or pain in the hip. In this material are included the long term follow-up of the first 4 cases reported by one of us in 1968. The follow-up in our series ranges from a few months to 15 years. The clinical sequelae are minimal at the moment: slight decrease of abduction and internal rotation. The radiological follow-up shows a slow disappearance of calcification, a premature fusion of the physis, a coxa magna, a broadening and shortening of the femoral neck. These residual radiological anomalies, in spite of a good clinical state at the moment, are worrying for future of these hips. The etiology is unknown, but these calcifications are acquired and there are good reasons to think they are iatrogenic, probably secondary to an inadvertent injection into the hip joint at the time of an intravenous femoral infusion of a drug toxic for the hip cartilage. It seems reasonable to avoid the femoral route for intravenous infusion of drugs in newborns and infants.

[Early diagnosis of staphylococcic infection in epidural space : radiologic contribution (author's transl)]. / Diagnostic précoce d'une épidurite staphylococcique. Apport de la radiologie.

Infection of the épidural space was demonstrated on clinic (cauda equina compression) and radiology. Three investigations are considered and compared : Dimer X radiculography, lumbar phlebography, duroliopaque myelography. The transfemoral arcending lumbar catheterization of the epidural veins precise the compression by staphylococcic external pachymeningitis. No liquid is introduced in cerebro spinal fluid : there is not risk of infectious arachnoiditis. Myelography with positive contrast (duroliopaque: ethyl monoiodostearate) is much attractive but it is a procedure not easy to perform, even badly tolerated by the patient. For these reasons the lumbar phlebography, easily performed, can be realised in first intention.