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1.
J Endocrinol Invest ; 41(9): 1075-1082, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29368139

ABSTRACT

AIMS: Women with gestational hyperglycemia commonly experience hypertensive disorders during pregnancy. More information is needed about how hypertension develops in these patients over time. We investigated the prevalence of hypertension during and 3 years after pregnancy in Caucasian women with gestational hyperglycemia. We also investigated metabolic syndrome presence, glucose tolerance status, insulin sensitivity and insulin secretion levels in the follow-up period. METHODS: In a prospective longitudinal study with a 3-year follow-up, we assessed hypertension status and clinical-related characteristics of 103 consecutive women with gestational hyperglycemia sub-grouped according to their hypertensive status during and after pregnancy. RESULTS: Overall, 29 (28.1%) women had hypertension during pregnancy (24 gestational hypertension; 4 chronic hypertension; 1 preeclampsia). At follow-up 16 (15.5%) women were diagnosed as having hypertension (11 with hypertension in pregnancy; 5 with a normotensive pregnancy). Women with hypertension after pregnancy had higher BMI, metabolic syndrome rate and worse insulin resistance indexes than normotensive women. Weight increase at follow-up (OR 1.17, 95% CI 1.00-1.35) and hypertension in pregnancy (OR 6.72, 95% CI 1.17-38.64) were associated with hypertension after pregnancy. CONCLUSIONS: Women with gestational hyperglycemia should undergo regular monitoring during and after pregnancy to detect metabolic and clinical impairments and to prevent cardiovascular harm.


Subject(s)
Blood Glucose/metabolism , Delivery, Obstetric/trends , Hyperglycemia/blood , Hyperglycemia/epidemiology , Hypertension, Pregnancy-Induced/blood , Hypertension, Pregnancy-Induced/epidemiology , Blood Pressure/physiology , Female , Follow-Up Studies , Humans , Hyperglycemia/diagnosis , Hypertension, Pregnancy-Induced/diagnosis , Longitudinal Studies , Pre-Eclampsia/blood , Pre-Eclampsia/diagnosis , Pre-Eclampsia/epidemiology , Pregnancy , Prospective Studies , Time Factors
2.
Musculoskelet Surg ; 100(3): 187-191, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27287544

ABSTRACT

INTRODUCTION: Acromioclavicular joint (ACJ) dislocation is a common injury that can result from sports activities. The surgical technique for the treatment of Type III and Type IV injuries, according to the Rockwood classification, remains controversial. The purpose of the study was to determine the functional outcome after minimally invasive and arthroscopic surgery. The mini-open surgery was done with MINAR® system, whereas the arthroscopic technique was done with Dog BoneTM Button. STUDY DESIGN: Retrospective Cohort study. METHODS: We reviewed 31 who were surgically treated for acute acromioclavicular dislocation Type III and Type IV (2012-2015). We excluded subjects with chronic dislocation or other injury. We selected 16 patients (average age 37).  Half of the sample patients were treated with mini-open surgery with the MINAR® system, and the other half of the patients were treated with the Dog Bone arthroscopic technique. The Constant Shoulder Score, the Oxford Shoulder Score, the Simple Shoulder Test and the Subjective Patient Outcome for Return to Sports (SPORTS) score were used to assess functional outcome of the treated shoulder. RESULTS: Mean follow-up was 13 months (range 6-27 months). The mean Constant Shoulder Score was 91.10 (range 82.76-96.66), Oxford Shoulder Score was 46.19 (range 42.00-48.00), the Simple Shoulder Test was 10.50 (range 9.00-12.00), and the SPORTS score was 7.88 (range 3-10). There is a statistically significant difference between the sample operated with the mini-open surgery and the group operated with arthroscopic technique. The probability of return to their sport, according to the results of the SPORTS score, was significantly higher for patients treated with the MINAR® system (p < 0.001). However, the objective parameter of Constant scale is statistically better in patients operated by arthroscopic technique (p < 0.05; p < 0.001). CONCLUSION: Restoration of ACJ anatomy is the key to a successful therapy. The surgical technique should be personalized. The miny-open surgery and also the arthroscopic surgery are adequate with good clinical results. However, according to the SPORTS score, the patients treated with mini-open surgery returned to their sport with less pain and better performance than those belonging to the other group.


Subject(s)
Acromioclavicular Joint/injuries , Arthroscopy , Joint Dislocations/surgery , Return to Sport , Adult , Arthroscopy/methods , Female , Follow-Up Studies , Humans , Joint Dislocations/diagnosis , Male , Middle Aged , Minimally Invasive Surgical Procedures/methods , Retrospective Studies , Trauma Severity Indices , Treatment Outcome
3.
Ultraschall Med ; 36(2): 174-86, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25429625

ABSTRACT

PURPOSE: Brain shift and tissue deformation during surgery for intracranial lesions are the main actual limitations of neuro-navigation (NN), which currently relies mainly on preoperative imaging. Ultrasound (US), being a real-time imaging modality, is becoming progressively more widespread during neurosurgical procedures, but most neurosurgeons, trained on axial computed tomography (CT) and magnetic resonance imaging (MRI) slices, lack specific US training and have difficulties recognizing anatomic structures with the same confidence as in preoperative imaging. Therefore real-time intraoperative fusion imaging (FI) between preoperative imaging and intraoperative ultrasound (ioUS) for virtual navigation (VN) is highly desirable. We describe our procedure for real-time navigation during surgery for different cerebral lesions. MATERIALS AND METHODS: We performed fusion imaging with virtual navigation for patients undergoing surgery for brain lesion removal using an ultrasound-based real-time neuro-navigation system that fuses intraoperative cerebral ultrasound with preoperative MRI and simultaneously displays an MRI slice coplanar to an ioUS image. RESULTS: 58 patients underwent surgery at our institution for intracranial lesion removal with image guidance using a US system equipped with fusion imaging for neuro-navigation. In all cases the initial (external) registration error obtained by the corresponding anatomical landmark procedure was below 2 mm and the craniotomy was correctly placed. The transdural window gave satisfactory US image quality and the lesion was always detectable and measurable on both axes. Brain shift/deformation correction has been successfully employed in 42 cases to restore the co-registration during surgery. The accuracy of ioUS/MRI fusion/overlapping was confirmed intraoperatively under direct visualization of anatomic landmarks and the error was < 3 mm in all cases (100 %). CONCLUSION: Neuro-navigation using intraoperative US integrated with preoperative MRI is reliable, accurate and user-friendly. Moreover, the adjustments are very helpful in correcting brain shift and tissue distortion. This integrated system allows true real-time feedback during surgery and is less expensive and time-consuming than other intraoperative imaging techniques, offering high precision and orientation.


Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/surgery , Imaging, Three-Dimensional/instrumentation , Imaging, Three-Dimensional/methods , Intraoperative Complications/diagnosis , Intraoperative Complications/surgery , Intraoperative Period , Magnetic Resonance Imaging, Interventional/instrumentation , Magnetic Resonance Imaging, Interventional/methods , Multimodal Imaging/instrumentation , Multimodal Imaging/methods , Neuronavigation/instrumentation , Neuronavigation/methods , Preoperative Care , Ultrasonography, Interventional/instrumentation , Ultrasonography, Interventional/methods , User-Computer Interface , Adolescent , Adult , Aged , Brain Neoplasms/secondary , Cerebral Cortex/pathology , Cerebral Cortex/surgery , Child , Craniotomy/instrumentation , Craniotomy/methods , Equipment Design , Female , Humans , Male , Middle Aged , Sensitivity and Specificity
4.
Musculoskelet Surg ; 97 Suppl 1: 15-22, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23588827

ABSTRACT

PURPOSE: This study aims to review the incidence of fibromyalgia in a cohort of patients who were treated for shoulder pain and address whether a concomitant fibromyalgia could have had detrimental effect on outcomes. METHODS: The treatment of 286 consecutive patients for shoulder pain was reviewed. RESULTS: Eighteen patients (6.3 %) were diagnosed as having fibromyalgia, but in 13 of them (72 %), the diagnosis was initially missed. Five patients received a total of 11 surgeries for treatment of the shoulder. At an average follow-up of 15 months (range 12-27), the average new Oxford shoulder score (OS score) was 49 % (range 6-87 %). The average physical component of the Short-Form-12 Healthy Survey (SF-12) was 36 (range 21-55), and the mental component 30 (range 15-46). The Summary Outcome Determination score (SOD score) was 1.3 (range-3 to 6). CONCLUSIONS: Fibromyalgia occurs relatively frequently in patients who complain of shoulder pain and it can be a cause of failure in the treatment of concomitant painful shoulder conditions.


Subject(s)
Fibromyalgia/complications , Fibromyalgia/epidemiology , Shoulder Pain/complications , Shoulder Pain/therapy , Aged , Algorithms , Female , Humans , Incidence , Male , Middle Aged , Treatment Failure
5.
Neuroscience ; 202: 131-46, 2012 Jan 27.
Article in English | MEDLINE | ID: mdl-22133892

ABSTRACT

Estradiol affects hippocampal-dependent spatial memory and underlying structural and electrical synaptic plasticity in female mice and rats. Using estrogen receptor (ER) alpha and beta knockout mice and wild-type littermates, we investigated the role of ERs in estradiol effects on multiple pathways important for hippocampal plasticity and learning. Six hours of estradiol administration increased immunoreactivity for phosphorylated Akt throughout the hippocampal formation, whereas 48 h of estradiol increased immunoreactivity for phosphorylated TrkB receptor. Estradiol effects on phosphorylated Akt and TrkB immunoreactivities were abolished in ER alpha and ER beta knockout mice. Estradiol also had distinct effects on immunoreactivity for post-synaptic density 95 (PSD-95) and brain derived-neurotrophic factor (BDNF) mRNA in ER alpha and beta knockout mice. Thus, estradiol acts through both ERs alpha and beta in several subregions of the hippocampal formation. The different effects of estradiol at 6 and 48 h indicate that several mechanisms of estrogen receptor signaling contribute to this female hormone's influence on hippocampal synaptic plasticity. By further delineating these mechanisms, we will better understand and predict the effects of endogenous and exogenous ovarian steroids on mood, cognition, and other hippocampal-dependent behaviors.


Subject(s)
Estradiol/pharmacology , Estrogen Receptor alpha/drug effects , Estrogen Receptor beta/drug effects , Hippocampus/drug effects , Neural Pathways/drug effects , Neuronal Plasticity/drug effects , Synapses/drug effects , Animals , Brain-Derived Neurotrophic Factor/biosynthesis , Brain-Derived Neurotrophic Factor/genetics , Data Interpretation, Statistical , Densitometry , Disks Large Homolog 4 Protein , Estrogen Receptor alpha/genetics , Estrogen Receptor beta/genetics , Estrous Cycle/drug effects , Estrous Cycle/physiology , Female , Guanylate Kinases/metabolism , Hippocampus/cytology , Hormone Replacement Therapy , Immunohistochemistry , In Situ Hybridization , Membrane Proteins/metabolism , Mice , Mice, Inbred C57BL , Mice, Knockout , Ovariectomy , Proto-Oncogene Proteins c-akt/metabolism , Receptor, trkB/biosynthesis , Receptor, trkB/genetics
6.
Exp Clin Endocrinol Diabetes ; 117(8): 373-7, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19536738

ABSTRACT

BACKGROUND: Hypertension is one of the major complications of pregnancy. Its impact in type 2 diabetic pregnant women could be understimated because it is generally evaluated by retrospective studies and as one of the outcome measures. OBJECTIVE: Our aims were: 1) to evaluate the prevalence of hypertensive disease between type 2 diabetic and normal pregnancies; 2) to relate hypertensive disease to body weight in type 2 diabetic pregnancies; 3) to assess the impact of different types of hypertension on pregnancy outcome in type 2 diabetic women. STUDY DESIGN: Seventy-six type 2 diabetic (23 normal-weight, 26 overweight and 27 obese) and sixty normal (43, 15 and 2 respectively; x (2) 0.0001) pregnancies, matched for age and smoking habit. Hypertension was defined as >/=140/90 mmHg and classified in chronic, gestational and pre-eclampsia. STATISTICAL ANALYSIS: Student's t-test, chi (2), simple, and/or multiple and logistic regression analysis were used when appropriate. Odds ratio was calculated for hypertension. p significant <0.05. RESULTS: The overall prevalence of hypertension was 40.8% (18.4% chronic, 17.1% gestational and 5.3% pre-eclampsia) in type 2 diabetic pregnancies and 10% (8.3% gestational and 1.7% pre-eclampsia) in normal pregnancies (p<0.0001), with an odds ratio of 6.2. All the types of hypertension, significantly chronic, contributed to the higher prevalence. Only in diabetic pregnancies, hypertension was associated with a higher pregestational BMI; whenever BMI increased, chronic and gestational hypertension increased by contrast of pre-eclampsia (chi (2), 0.02). Hypertensive disorders did not affect maternal-fetal outcome. CONCLUSIONS: The prevalence of hypertension was 40.8% in type 2 diabetic pregnant women whilst it was 10.0% in non diabetic controls. All hypertensive disorders, significantly chronic, were more frequent. Increasing BMI was a crucial factor for chronic and gestational but not for pre-eclampsia. Hypertensive diseases did not seem to affect pregnancy outcome.


Subject(s)
Diabetes Mellitus, Type 2/complications , Hypertension, Pregnancy-Induced/epidemiology , Hypertension/epidemiology , Obesity/complications , Adult , Body Mass Index , Chi-Square Distribution , Female , Humans , Hypertension/complications , Hypertension, Pregnancy-Induced/etiology , Odds Ratio , Patient Selection , Pregnancy , Pregnancy Outcome , Prevalence , Prospective Studies , Regression Analysis , Smoking
7.
Vet Rec ; 158(4): 125-9, 2006 Jan 28.
Article in English | MEDLINE | ID: mdl-16443838

ABSTRACT

Two-dimensional real-time, M-mode and Doppler echocardiographic measurements were made in 11 adult wolves (Canis lupus) anaesthetised with an intramuscular combination of medetomidine, ketamine, butorphanol and acepromazine followed by isoflurane in oxygen. M-mode measurements of the left ventricle, B-mode measurements of the left atrium and aorta, systolic indices, and Doppler measurements of aortic and pulmonary blood outflow, and of mitral and tricuspid blood inflow, were recorded. The values obtained were compared with those reported for dogs of similar bodyweight and body type. The diastolic measurements of the cardiac chambers and walls were similar to those reported for healthy, conscious dogs, but the use of anaesthesia probably resulted in the markedly different systolic cardiac measurements, systolic indices and Doppler blood flow velocities observed in the wolves. Mild mitral regurgitation, probably due to mitral endocardiosis, was observed in one wolf, and trivial functional mitral insufficiency was observed in five others.


Subject(s)
Conscious Sedation/veterinary , Echocardiography, Doppler/veterinary , Echocardiography/veterinary , Heart/physiology , Hemodynamics/physiology , Wolves/physiology , Animals , Animals, Wild , Blood Flow Velocity/veterinary , Female , Heart/anatomy & histology , Male , Reference Values
8.
Ann Chir Plast Esthet ; 48(1): 20-30, 2003 Feb.
Article in French | MEDLINE | ID: mdl-12657331

ABSTRACT

INTRODUCTION: Secondary bone grafting of the maxilla has become a well-accepted procedure in the surgical protocol for rehabilitation of patients with cleft lip and palate (CLP). The aim of this study is to review the surgical procedure and the indication of the secondary bone graft. MATERIALS AND METHODS: Sixty-two secondary bone graft were retrospectively reviewed from 1993 to 2000. There were 50 unilateral CLP and 12 bilateral CLP. The age at the time of bone grafting ranged from 9 years to 25.5 years with a mean at 14.34 +/- 2.9 years. The same operator performed a Gingivoperiosteoplasty (GPO) in all cases and the graft material was cancellous iliac bone in all cases. RESULTS: There were three indications of the bone graft and in each case the objective is different. First the interceptive bone graft in mixed dentition (50%): it was performed prior to the orthodontic treatment 12.8 +/- 2.3 years. The graft provides a bone support for teeth adjacent to the cleft. Second the stabilisation bone graft in permanent dentition (33.8%): it stabilize the orthodontic treatment and/or plan orthognathic surgery (15.2 +/- 1.6 years). Third the consolidation bone graft (16.2%): it was a late secondary bone graft after the complete growth (17,3 +/- 3,6 years) to correct the sequellae. It restored the maxilla continuity, stabilised the clefting teeth and prepared a prosthetic rehabilitation. CONCLUSION: The benefice of the secondary bone graft with GPO are numerous and is a part of the protocol treatment in CLP patients. A multidisciplinary follow up is necessary for the indication and timing of secondary bone grafting. The indication is subject to the clefting teeth, to the occlusal status and to the maxillary growth.


Subject(s)
Cleft Lip/surgery , Cleft Palate/surgery , Gingivoplasty/methods , Maxilla/transplantation , Plastic Surgery Procedures/methods , Adolescent , Adult , Child , Cleft Lip/pathology , Cleft Palate/pathology , Female , Humans , Male , Orthodontics, Corrective , Reoperation , Retrospective Studies , Treatment Outcome
9.
Ann Chir Plast Esthet ; 47(2): 143-9, 2002 Apr.
Article in French | MEDLINE | ID: mdl-12064203

ABSTRACT

Management of labio-maxillo-palatine clefts has two major requirements: to constitute a multidisciplinary staff (surgical, phonological, orthodontical) intervening as soon as possible and determination of a precise therapeutical chronology not only for primary surgery but also for sequellae. Primary surgical protocol is in cases of total clefts these defined by Malek and Psaume; and for pure labial or incomplete clefts, we perform a neonatal surgery. Integration of interceptive correction of sequellae into thus protocol appears basic: correction of alveolar cleft by gingivoplasty (5 to 7 years) associated with secondary home-graft between 11 to 13 years; early nasal revision since 2 years for functional and aesthetic reasons. Early control of speech development, otologic problems and their management appears a very important point. Introduction of the concept of maxillary distraction appears to us a very important improvement for correcting orthognatic cases with major problems of squeletical growth. Recent introduction of the antenatal diagnosis introduces a new concept in psychological approach of these cases. It is necessary to establish a network for managing these cases since the antenatal period.


Subject(s)
Cleft Lip/surgery , Cleft Palate/surgery , Plastic Surgery Procedures/methods , Academic Medical Centers , Adolescent , Child , Child, Preschool , France , Humans , Infant , Infant, Newborn
10.
J Neurosci ; 21(19): 7517-25, 2001 Oct 01.
Article in English | MEDLINE | ID: mdl-11567041

ABSTRACT

Contactin (also known as F3, F11) is a surface glycoprotein that has significant homology with the beta2 subunit of voltage-gated Na(+) channels. Contactin and Na(+) channels can be reciprocally coimmunoprecipitated from brain homogenates, indicating association within a complex. Cells cotransfected with Na(+) channel Na(v)1.2alpha and beta1 subunits and contactin have threefold to fourfold higher peak Na(+) currents than cells with Na(v)1.2alpha alone, Na(v)1.2/beta1, Na(v)1.2/contactin, or Na(v)1.2/beta1/beta2. These cells also have a correspondingly higher saxitoxin binding, suggesting an increased Na(+) channel surface membrane density. Coimmunoprecipitation of different subunits from cell lines shows that contactin interacts specifically with the beta1 subunit. In the PNS, immunocytochemical studies show a transient colocalization of contactin and Na(+) channels at new nodes of Ranvier forming during remyelination. In the CNS, there is a particularly high level of colocalization of Na(+) channels and contactin at nodes both during development and in the adult. Contactin may thus significantly influence the functional expression and distribution of Na(+) channels in neurons.


Subject(s)
Cell Adhesion Molecules, Neuronal/metabolism , Sodium Channels/metabolism , Animals , Axons/metabolism , Axons/pathology , Binding, Competitive/drug effects , Brain Chemistry , CHO Cells , Cell Adhesion Molecules, Neuronal/genetics , Cell Line , Cell Membrane/chemistry , Cell Membrane/metabolism , Contactins , Cricetinae , Demyelinating Diseases/chemically induced , Demyelinating Diseases/pathology , Female , Gene Expression , Lysophosphatidylcholines/pharmacology , NAV1.2 Voltage-Gated Sodium Channel , Nerve Tissue Proteins/antagonists & inhibitors , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Patch-Clamp Techniques , Precipitin Tests , Protein Subunits , Ranvier's Nodes/metabolism , Rats , Saxitoxin/metabolism , Saxitoxin/pharmacokinetics , Sciatic Nerve/drug effects , Sciatic Nerve/pathology , Sodium/metabolism , Sodium Channel Blockers , Sodium Channels/genetics , Tetrodotoxin/pharmacology , Transfection
11.
Circulation ; 103(9): 1303-10, 2001 Mar 06.
Article in English | MEDLINE | ID: mdl-11238277

ABSTRACT

BACKGROUND: Sodium channels isolated from mammalian brain are composed of alpha-, beta(1)-, and beta(2)-subunits. The composition of sodium channels in cardiac muscle, however, has not been defined, and disagreement exists over which beta-subunits are expressed in the myocytes. Some investigators have demonstrated beta(1) expression in heart. Others have not detected any auxiliary subunits. On the basis of Northern blot analysis of total RNA, beta(2) expression has been thought to be exclusive to neurons and absent from cardiac muscle. METHODS AND RESULTS: The goal of this study was to define the subunit composition of cardiac sodium channels in myocytes. We show that cardiac sodium channels are composed of alpha-, beta(1)-, and beta(2)-subunits. Nav1.5 and Nav1.1 are expressed in myocytes and are associated with beta(1)- and beta(2)-subunits. Immunocytochemical localization of Nav1.1, beta(1), and beta(2) in adult heart sections showed that these subunits are expressed at the Z lines, as shown previously for Nav1.5. Coexpression of Nav1.5 with beta(2) in transfected cells resulted in no detectable changes in sodium current. CONCLUSIONS: Cardiac sodium channels are composed of alpha- (Nav1.1 or Nav1.5), beta(1)-, and beta(2)-subunits. Although beta(1)-subunits modulate cardiac sodium channel current, beta(2)-subunit function in heart may be limited to cell adhesion.


Subject(s)
Myocardium/metabolism , Sodium Channels/physiology , Animals , Animals, Newborn , Antibody Specificity , Brain/metabolism , Cell Line , Electrophysiology , Fluorescent Antibody Technique , Humans , Mice , Myocardium/cytology , Protein Subunits , RNA, Messenger/genetics , RNA, Messenger/metabolism , Rats , Reverse Transcriptase Polymerase Chain Reaction , Sodium Channels/genetics , Sodium Channels/immunology
12.
J Biol Chem ; 275(2): 1079-88, 2000 Jan 14.
Article in English | MEDLINE | ID: mdl-10625649

ABSTRACT

Auxiliary beta1 subunits of voltage-gated sodium channels have been shown to be cell adhesion molecules of the Ig superfamily. Co-expression of alpha and beta1 subunits modulates channel gating as well as plasma membrane expression levels. We have cloned, sequenced, and expressed a splice variant of beta1, termed beta1A, that results from an apparent intron retention event. beta1 and beta1A are structurally homologous proteins with type I membrane topology; however, they contain little to no amino acid homology beyond the shared Ig loop region. beta1A mRNA expression is developmentally regulated in rat brain such that it is complementary to beta1. beta1A mRNA is expressed during embryonic development, and then its expression becomes undetectable after birth, concomitant with the onset of beta1 expression. In contrast, beta1A mRNA is expressed in adult adrenal gland and heart. Western blot analysis revealed beta1A protein expression in heart, skeletal muscle, and adrenal gland but not in adult brain or spinal cord. Immunocytochemical analysis of beta1A expression revealed selective expression in brain and spinal cord neurons, with high expression in heart and all dorsal root ganglia neurons. Co-expression of alphaIIA and beta1A subunits in Chinese hamster lung 1610 cells results in a 2.5-fold increase in sodium current density compared with cells expressing alphaIIA alone. This increase in current density reflected two effects of beta1A: 1) an increase in the proportion of cells expressing detectable sodium currents and 2) an increase in the level of functional sodium channels in expressing cells. [(3)H]Saxitoxin binding analysis revealed a 4-fold increase in B(max) with no change in K(D) in cells coexpressing alphaIIA and beta1A compared with cells expressing alphaIIA alone. beta1A-expressing cell lines also revealed subtle differences in sodium channel activation and inactivation. These effects of beta1A subunits on sodium channel function may be physiologically important events in the development of excitable cells.


Subject(s)
Adrenal Glands/metabolism , Gene Expression Regulation, Developmental , Introns , Sodium Channels/genetics , Sodium Channels/physiology , Amino Acid Sequence , Animals , Cell Line , Cloning, Molecular , Cricetinae , Cricetulus , Embryonic and Fetal Development , Fetus , Ganglia, Spinal/metabolism , Macromolecular Substances , Models, Molecular , Molecular Sequence Data , Muscle, Skeletal/metabolism , Myocardium/metabolism , Neurons/metabolism , Protein Structure, Secondary , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Sequence Homology, Amino Acid , Sodium Channels/chemistry , Transfection
13.
J Biol Chem ; 274(37): 26511-7, 1999 Sep 10.
Article in English | MEDLINE | ID: mdl-10473612

ABSTRACT

Voltage-gated sodium channels isolated from mammalian brain are composed of alpha, beta1, and beta2 subunits. The alpha subunit forms the ion conducting pore of the channel, whereas the beta1 and beta2 subunits modulate channel function, as well as channel plasma membrane expression levels. beta1 and beta2 each contain a single, extracellular Ig-like domain with structural similarity to the neural cell adhesion molecule (CAM), myelin Po. beta2 contains strong amino acid homology to the third Ig domain and to the juxtamembrane region of F3/contactin. Many CAMs of the Ig superfamily have been shown to interact with extracellular matrix molecules. We hypothesized that beta2 may interact with tenascin-R (TN-R), an extracellular matrix molecule that is secreted by oligodendrocytes during myelination and that binds F3-contactin. We show here that cells expressing sodium channel beta1 or beta2 subunits are functionally modulated by TN-R. Transfected cells stably expressing beta1 or beta2 subunits initially recognized and then were repelled from TN-R substrates. The cysteine-rich amino-terminal domain of TN-R expressed as a recombinant peptide, termed EGF-L, appears to be responsible for the repellent effect on beta subunit-expressing cells. The epidermal growth factor-like repeats and fibronectin-like repeats 6-8 are most effective in the initial adhesion of beta subunit-expressing cells. Application of EGF-L to alphaIIAbeta1beta2 channels expressed in Xenopus oocytes potentiated expressed sodium currents without significantly altering current time course or the voltage dependence of current activation or inactivation. Thus, sodium channel beta subunits appear to function as CAMs, and TN-R may be an important regulator of sodium channel localization and function in neurons.


Subject(s)
Sodium Channels/metabolism , Tenascin/metabolism , Amino Acid Sequence , Animals , Cell Adhesion , Cell Line , Cricetinae , Cricetulus , Epidermal Growth Factor/metabolism , Mice , Molecular Sequence Data , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sodium Channels/chemistry , Tenascin/chemistry , Tenascin/genetics , Transfection , Xenopus
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