RESUMO
AIMS: Transseptal puncture (TSP) has become a common approach in catheter ablation of arrhythmia originating from the left atrium. In paediatric patients, however, TSP can be a challenge due to narrower access vessels and small left atrial size, and the safety of TSP in smaller children is yet to be understood. The purpose of this study was to retrospectively evaluate the feasibility and safety of TSP in children weighing below 30 kg. METHODS AND RESULTS: Among 655 paediatric patients who underwent catheter ablation of arrhythmia between July 2009 and April 2015, 43 cases having structurally normal hearts, weighing <30 kg and requiring TSP were included in the study. Age, height, body weight, diagnosis, and complications during TSP and catheter ablation were evaluated. The median age, height, and body weight (range) were 7.0 years (0.3-11.1), 116.8 cm (54.0-138.4 cm) and 21.5 kg (4.3-29.6 kg), respectively. Diagnosis included manifest (n = 27; 62.8%) and concealed accessory pathway (n = 14; 32.6%) and atrial tachycardia (n = 2; 4.6%). In 10 cases (23.2%), TSP using radiofrequency energy was performed. None of the patients had major complications. Pericardial effusion was recorded as a minor complication in one patient (2.3%). CONCLUSION: TSP was feasible, safe, and of low risk of complications in children weighing <30 kg.
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Arritmias Cardíacas/cirurgia , Peso Corporal , Ablação por Cateter , Septos Cardíacos/cirurgia , Punções/métodos , Procedimentos Cirúrgicos Cardíacos , Pré-Escolar , Ecocardiografia , Feminino , Átrios do Coração/anatomia & histologia , Humanos , Lactente , Japão , Masculino , Derrame Pericárdico/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND: In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old. METHODS: This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients <18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed. RESULTS: A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase. CONCLUSIONS: Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.
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Desfibriladores Implantáveis , Adulto , Humanos , Criança , Adolescente , Estudos Retrospectivos , Resultado do Tratamento , Desfibriladores Implantáveis/efeitos adversos , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Arritmias CardíacasRESUMO
OBJECTIVE: The left superior vena cava (LSVC) is often complicated with congenital heart defect. Although we simply clamp LSVC during cardio-pulmonary bypass (CPB), appropriateness of this technique has not been clarified. We noninvasively evaluate cerebral tissue oxygenation while the clamping of LSVC under CPB by near-infrared spectroscopy (NIRS). METHODS: Six children (3 male and 3 female; aged 1.0 +/- 0.6 year) undergoing open heart surgery were studied. The NIRO 300 was incorporated into an established multimodal monitoring system. Tissue oxygenation index (TOI), oxyhemoglobin (O2Hb), and deoxyhemoglobin (HHb) changes were assessed and compared with LSVC pressure. RESULTS: There were no significant changes in cerebral oxygen delivery after LSVC clamp. LSVC pressure increased from 7.3 +/- 1.8 mmHg to 20.1 +/- 2.6 just after LSVC clamp, but gradually decreased without any maneuver. CONCLUSION: These data demonstrated that LSVC could be safely clamped when LSVC pressure was under 30 mmHg.
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Circulação Cerebrovascular/fisiologia , Veia Cava Superior/fisiologia , Constrição , Feminino , Cardiopatias Congênitas , Humanos , Lactente , Masculino , Oxigênio/sangue , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Background: Disease understanding in patients with congenital heart disease is important in transitional and lifelong care. This study aimed to develop the Japanese version of the Leuven Knowledge Questionnaire for Congenital Heart Disease (LKQCHD) and identify factors associated with disease-related knowledge. MethodsâandâResults: After confirming the content and face validity of the scale, a questionnaire including the LKQCHD was distributed to 59 eligible patients aged >16 years attending a university hospital. For the 58 participants who responded (30 males, 28 females; median age 22 years), the mean (±SD) LKQCHD total score was 53.7±15.4, with mean (±SD) scores for each domain as follows: Disease and Treatment, 68.3±19.7; Preventing Complications, 45.8±19.0; Physical Activity, 74.1±34.1; Sex and Heredity, 37.9±35.4; and Contraception and Pregnancy, 40.2±29.1. Regarding known-groups validity, we found a positive correlation between the LKQCHD score and age (ρ=0.268, P=0.042), and a significantly low LKQCHD score in the moderate/severe disease group (η2=0.131, P=0.021). Regarding convergent validity, the LKQCHD score was positively correlated with the total and subscale scores of the Resilience Assessment Tool (r=0.213 [P=0.109] and r=0.405 [P=0.002], respectively). Conclusions: We confirmed the validity of the Japanese version of the LKQCHD, concluding that patient education regarding long-term complications, prevention methods, heredity, pregnancy, and childbirth is needed.
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BACKGROUND: In the treatment of adult congenital heart disease (ACHD), the transfer of patients from pediatric cardiologists to ACHD cardiologists is of relevance. However, little is known about the clinical courses of ACHD patients that have been referred by non-CHD-specialized doctors (n-CSDs). METHODS: This retrospective cohort study included 230 patients (average age: 37 ± 15.2 years, male: 97) who were referred to a single specialized ACHD center between April 2016 and July 2019. We compared the characteristics and clinical courses between patients referred by n-CSDs and those referred by CHD-specialized-doctors (CSDs). RESULTS: Overall, 121 (53%) patients were referred by n-CSDs. Among them, 91 (75%) patients were referred by adult cardiologists. Univariate analysis showed that the patients referred by n-CSDs were older than those referred by CSDs (41.6 ± 16.3 vs. 32.0 ± 12.0 years, p < 0.01), were more likely to have simple CHD, and less likely to have severe CHD (27.0% vs. 12.8% and 16.5% vs. 40.4%, respectively, p < 0.01). Patients referred by n-CSDs were also more likely to have a history of loss of follow-up (16.5% vs. 3.7%, p < 0.01) and to require invasive treatments after referral, including cardiac surgeries and transcatheter interventions (47.9% vs. 26.6 %, p < 0.01). Notably, unintended invasive treatments that were not designated by the referring doctors were more frequently required in patients with moderate complexity referred by n-CSDs (50.0% vs. 23.3%, p = 0.02). CONCLUSIONS: Patients with moderate CHD complexity referred by n-CSDs are more likely to require unintended invasive treatments. Referrals to specialized ACHD centers may be most beneficial for these patients.
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Cardiologistas/estatística & dados numéricos , Medicina Geral/estatística & dados numéricos , Cardiopatias Congênitas/terapia , Encaminhamento e Consulta/estatística & dados numéricos , Transição para Assistência do Adulto/estatística & dados numéricos , Adolescente , Adulto , Humanos , Perda de Seguimento , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
BACKGROUND: Although pediatric catheter ablation therapy has often been described, few reports on outcomes in a large series of patients at a single center are available. OBJECTIVE: The purpose of this study was to evaluate arrhythmia substrates, outcomes, and complications of catheter ablation in children and patients with congenital heart disease (CHD) performed at a single center. METHODS: We retrospectively analyzed all pediatric patients <18 years and patients of all ages with CHD who underwent ablation therapy between June 2006 and May 2018. RESULTS: A total of 1021 ablation procedures were performed in 877 patients (median age 12.5 years; range 2 months to 67 years). This cohort included 152 CHD patients, 90 small patients (<15 kg), and 14 infants (<1 year). The most frequent indication was Wolff-Parkinson-White pattern (WPW) (n = 287 [32.7%]). Of the 55 patients with asymptomatic WPW, 40 patients (72.7%) had retrograde accessory pathway conduction. Overall success and recurrence rates were 93.5% and 17.3%, respectively. Small patients and CHD patients had lower success rates. No deaths occurred. Serious complications occurred in 5 patients. CONCLUSION: Catheter ablation is safe and effective for treatment of arrhythmia in pediatric and CHD patients. However, ablation was less successful in small patients and CHD patients. The risk of complications was similar to those previously reported for catheter ablation in pediatric, CHD, and adult patients.
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Feixe Acessório Atrioventricular/cirurgia , Arritmias Cardíacas/cirurgia , Ablação por Cateter/métodos , Cardiopatias Congênitas/complicações , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Feixe Acessório Atrioventricular/fisiopatologia , Adolescente , Adulto , Idoso , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/fisiopatologia , Mapeamento Potencial de Superfície Corporal , Criança , Pré-Escolar , Feminino , Cardiopatias Congênitas/fisiopatologia , Humanos , Imageamento Tridimensional , Lactente , Japão , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Potassium (K+) channel subunits of the Kv3 subfamily (Kv3.1-Kv3.4) display a positively shifted voltage dependence of activation and fast activation/deactivation kinetics when compared with other voltage-gated K+ channels, features that confer on Kv3 channels the ability to accelerate the repolarization of the action potential (AP) efficiently and specifically. In the cortex, the Kv3.1 and Kv3.2 proteins are expressed prominently in a subset of GABAergic interneurons known as fast-spiking (FS) cells and in fact are a significant determinant of the fast-spiking discharge pattern. However, in addition to expression at FS cell somata, Kv3.1 and Kv3.2 proteins also are expressed prominently at FS cell terminals, suggesting roles for Kv3 channels in neurotransmitter release. We investigated the effect of 1.0 mM tetraethylammonium (TEA; which blocks Kv3 channels) on inhibitory synaptic currents recorded in layer II/III neocortical pyramidal cells. Spike-evoked GABA release by FS cells was enhanced nearly twofold by 1.0 mM TEA, with a decrease in the paired pulse ratio (PPR), effects not reproduced by blockade of the non-Kv3 subfamily K+ channels also blocked by low concentrations of TEA. Moreover, in Kv3.1/Kv3.2 double knock-out (DKO) mice, the large effects of TEA were absent, spike-evoked GABA release was larger, and the PPR was lower than in wild-type mice. Together, these results suggest specific roles for Kv3 channels at FS cell terminals that are distinct from those of Kv1 and large-conductance Ca2+-activated K+ channels (also present at the FS cell synapse). We propose that at FS cell terminals synaptically localized Kv3 channels keep APs brief, limiting Ca2+ influx and hence release probability, thereby influencing synaptic depression at a synapse designed for sustained high-frequency synaptic transmission.
Assuntos
Neocórtex/citologia , Neurônios/metabolismo , Canais de Potássio/fisiologia , Sinapses/fisiologia , Transmissão Sináptica/fisiologia , Ácido gama-Aminobutírico/metabolismo , Potenciais de Ação/efeitos dos fármacos , Potenciais de Ação/fisiologia , Potenciais de Ação/efeitos da radiação , Aminopiridinas/farmacologia , Animais , Animais Recém-Nascidos , Cálcio/metabolismo , Diagnóstico por Imagem/métodos , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Esquema de Medicação , Interações Medicamentosas , Estimulação Elétrica/métodos , Técnicas In Vitro , Camundongos , Inibição Neural/efeitos dos fármacos , Inibição Neural/fisiologia , Inibição Neural/efeitos da radiação , Neurônios/citologia , Técnicas de Patch-Clamp/métodos , Peptídeos/farmacologia , Fótons , Bloqueadores dos Canais de Potássio/farmacologia , Sinapses/efeitos dos fármacos , Transmissão Sináptica/efeitos dos fármacos , Tetraetilamônio/farmacologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
BACKGROUND: Warfarin dosage requirements show considerable inter-individual variability. There are some reports of warfarin dose regimens correlating with single nucleotide polymorphisms (SNP) for CYP2C9, VKORC1 and other genes in adults. In children, however, reports are scarcer than in adults and the number of genes examined is more limited. We explored the effects of genetic variation on warfarin dose requirement in Japanese pediatric patients. METHODS: A total of 45 patients who were prescribed warfarin at the Yokohama City University Hospital were included in this study. The influence of genetic polymorphisms on stable warfarin dosage requirement was investigated by genotyping SNPs of the VKORC1, CYP2C9, CYP4F2, and GGCX genes (rs9923231, rs1057910, rs2108622, and rs699664, respectively) in each patient. RESULTS: Patients with the TT genotype in rs9923231 in VKORC1 required significantly lower maintenance dosages than those with the TC genotype (p = 0.001). Multiple regression analysis showed that, while VKORC1 status and patient height account for 78.2 % of the variability in maintenance warfarin dosage, genetic polymorphisms in VKORC1 account for 27 %, although polymorphisms in CYP4F2 and GGCX had no effect on dosage and the effect of CYP2C9 could not be evaluated. CONCLUSIONS: Polymorphisms in VKORC1 partially affected daily warfarin dosage requirements. VKORC1 genotype and height are the primary determinants influencing warfarin dosage in Japanese pediatric patients. Further studies with larger sample sizes are needed to confirm our results.
Assuntos
Citocromo P-450 CYP2C9/genética , Família 4 do Citocromo P450/genética , Variantes Farmacogenômicos , Polimorfismo de Nucleotídeo Único , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Adolescente , Adulto , Alelos , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Povo Asiático/genética , Criança , Pré-Escolar , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Lactente , Japão , Masculino , Varfarina/efeitos adversos , Adulto JovemRESUMO
The aim of this study is to clarify the fiber distribution of the nucleus reticularis magnocellularis (NRMC) and adjacent areas in the rat spinal cord. Biotinylated dextran amine was injected iontophoretically through a glass capillary into the areas, in which a single cell responded to noxious electrical stimulation of the sciatic nerve and to a pinch of the thigh skin with multiple spikes. Labeled fibers descended bilaterally through the ventral funiculi of the medulla oblongata and then through the ventral and lateral funiculi of the cervical cord with an ipsilateral predominance, and terminated in the spinal gray (laminae I-X). A single fiber sometimes ran through several laminae while bifurcating many short branches with axon varicosities and terminal buttons in one transverse section, that is, through laminae V, VII and X, through laminae V, IIl-IV and I-II, and through laminae VII to I-II. The present study showed that the wide distribution of a single fiber and a mass of fibers descending from the NRMC and adjacent areas might modulate not only somatic sensory and motor functions but also autonomic functions in the spinal cord.
Assuntos
Axônios/ultraestrutura , Biotina/análogos & derivados , Vias Eferentes/citologia , Bulbo/citologia , Dor/fisiopatologia , Formação Reticular/citologia , Medula Espinal/citologia , Potenciais de Ação/fisiologia , Vias Aferentes/fisiologia , Animais , Axônios/fisiologia , Dextranos , Vias Eferentes/fisiologia , Estimulação Elétrica , Lateralidade Funcional/fisiologia , Bulbo/fisiologia , Condução Nervosa/fisiologia , Nociceptores/fisiologia , Terminações Pré-Sinápticas/fisiologia , Terminações Pré-Sinápticas/ultraestrutura , Ratos , Tempo de Reação , Formação Reticular/fisiologia , Medula Espinal/fisiologiaRESUMO
Dihydrochalcones are a family of bicyclic flavonoids, defined by the presence of two benzene rings joined by a saturated three carbon bridge. In the present study, we systematically examined the antioxidant activities of dihydrochalcones against the stable free radical (1,1-diphenyl-2-picrylhydrazyl) and lipid peroxidation in the erythrocyte membrane. All dihydrochalcones exhibited higher antioxidant activities than the corresponding flavanones. The (1)H NMR analysis indicated that the active dihydrochalcone has a time-averaged conformation in which the aromatic A ring is orthogonal to the carbonyl group, while the inactive dihydrochalcone such as 2'-O-methyl-phloretin has a strongly hydrogen-bonded phenolic hydroxyl group, suggestive of a coplanar conformation. A hydroxyl group at the 2'-position of the dihydrochalcone A ring, newly formed by reduction of the flavanone C ring, is an essential pharmacophore for its radical scavenging potential.
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Antioxidantes/farmacologia , Chalcona/análogos & derivados , Chalcona/farmacologia , Flavanonas , Sequestradores de Radicais Livres/farmacologia , Compostos de Bifenilo , Chalcona/química , Chalconas , Membrana Eritrocítica/química , Flavonoides/farmacologia , Ligação de Hidrogênio , Hidroxilação , Peroxidação de Lipídeos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Picratos/química , Relação Estrutura-AtividadeRESUMO
We sought to measure infinitesimal phase response curves (iPRCs) from rat hippocampal CA1 pyramidal neurons. It is difficult to measure iPRCs from noisy neurons because of the dilemma that either the linearity or the signal-to-noise ratio of responses to external perturbations must be sacrificed. To overcome this difficulty, we used an iPRC measurement model formulated as the Langevin phase equation (LPE) to extract iPRCs in the Bayesian scheme. We then simultaneously verified the effectiveness of the measurement model and the reliability of the estimated iPRCs by demonstrating that LPEs with the estimated iPRCs could predict the stochastic behaviors of the same neurons, whose iPRCs had been measured, when they were perturbed by periodic stimulus currents. Our results suggest that the LPE is an effective model for real oscillating neurons and that many theoretical frameworks based on it may be applicable to real nerve systems.
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Potenciais de Ação/fisiologia , Algoritmos , Eletroencefalografia/métodos , Modelos Neurológicos , Reconhecimento Automatizado de Padrão/métodos , Células Piramidais/fisiologia , Animais , Simulação por Computador , Modelos Estatísticos , RatosRESUMO
For many years pathologists have used Hematoxylin and Eosin (H&E), single marker immunohistochemistry (IHC) and in situ hybridization with manual analysis by microscopy or at best simple digital imaging. There is a growing trend to update pathology to a digital workflow to improve objectivity and productivity, as has been done in radiology. There is also a need for tissue-based multivariate biomarker assays to improve the accuracy of diagnostic, prognostic, and predictive testing. Multivariate tests are not compatible with the traditional single marker, manual analysis pathology methods but instead require a digital platform with brightfield and fluorescence imaging, quantitative image analysis, and informatics. Here we describe the use of the Hamamatsu NanoZoomer Digital Pathology slide scanner with HCImage software for combined brightfield and multiplexed fluorescence biomarker analysis and highlight its applications in biomarker research and pathology testing. This combined approach will be an important aid to pathologists in making critical diagnoses.
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The six-layered mammalian neocortex evolved from the three-layered paleocortex, which is retained in present-day reptiles such as the turtle. Thus the turtle offers an opportunity to examine which cellular and circuit properties are fundamental to cortical function. We characterized the dendritic properties of pyramidal neurons in different cortical regions of mature turtles, Pseudemys scripta elegans, using whole cell recordings and calcium imaging from the axon, soma, and dendrites in a slice preparation. The firing properties, in response to intrasomatic depolarization, resembled those previously recorded with sharp electrodes in this preparation. Somatic spikes led to active backpropagating high-amplitude dendritic action potentials and intracellular calcium ion concentration ([Ca2+]i) changes at all dendritic locations, suggesting that both backpropagation and dendritic voltage-gated Ca2+ channels are primitive traits. We found no indication that Ca2+ spikes could be evoked in the dendrites, but fast Na+ spikes could be initiated there following intradendritic stimulation. Several lines of evidence indicate that fast, smaller-amplitude somatic spikes ("prepotentials") that are easily recorded in this preparation are generated in the axon. Most synaptically activated [Ca2+]i changes resulted from Ca2+ entry through voltage-gated channels. In some cells synaptic stimulation evoked a delayed Ca2+ wave due to release from internal stores following activation of metabotropic glutamate receptors. With some small differences these properties resemble those of pyramidal neurons in mammalian species. We conclude that spike backpropagation, dendritic Ca2+ channels, and synaptically activated Ca2+ release are primitive and conserved features of cortical pyramidal cells, and therefore likely fundamental to cortical function.
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Dendritos/fisiologia , Células Piramidais/citologia , Tartarugas/anatomia & histologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Encéfalo/citologia , Cálcio/metabolismo , Cicloleucina/análogos & derivados , Cicloleucina/farmacologia , Dendritos/efeitos dos fármacos , Dendritos/efeitos da radiação , Relação Dose-Resposta à Radiação , Estimulação Elétrica , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Potenciais Pós-Sinápticos Excitadores/fisiologia , Potenciais Pós-Sinápticos Excitadores/efeitos da radiação , Técnicas In Vitro , Técnicas de Patch-Clamp , Células Piramidais/efeitos dos fármacos , Células Piramidais/fisiologia , Sódio/metabolismo , Tartarugas/fisiologiaRESUMO
Repetitive synaptic stimulation in the stratum radiatum (SR) evokes large amplitude Ca2+ waves in the thick apical dendrites of hippocampal CA1 pyramidal neurons. These waves are initiated by activation of metabotropic glutamate receptors (mGluRs), which mobilize inositol-1,4,5-trisphospate (IP3) and release Ca2+ from intracellular stores. We explored mechanisms that modulate the spatial properties of these waves. Higher stimulus current evoked waves of increasing spatial extent. Most waves did not propagate through the soma; the majority stopped close to the junction of the soma and apical dendrite. Pairing strong stimulation with one electrode and subthreshold stimulation with another (associative activation) extended the waves distally but failed to extend waves into the cell body. Pairing synaptic stimulation with backpropagating action potentials enhanced the likelihood of wave generation but did not extend the waves to the somatic region. Priming the stores with Ca2+ entry through voltage dependent channels modulated wave properties but did not extend them past the dendrites. These results are consistent with propagation failing due to the dilution of synaptically generated IP3 as it diffuses into the large volume of the soma (impedance mismatch). Synaptically activating waves in the presence of low concentrations of carbachol, which probably increased the tonic level of IP3 throughout the cell, enhanced the extent of propagation and generated waves that invaded the soma, as long as low-affinity indicators were used to detect the [Ca2+]i changes. Consistent with this explanation direct injection of IP3 into the soma promoted wave propagation into this region. Ca2+ waves that propagated through the cell body were interesting because they did not fill the volume of the soma, but passed through the centre, often with large amplitude. These waves may be particularly effective in activating gene expression and protein synthesis.
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Potenciais de Ação/fisiologia , Cálcio/metabolismo , Dendritos/metabolismo , Células Piramidais/metabolismo , Potenciais de Ação/efeitos dos fármacos , Animais , Carbacol/farmacologia , Agonistas Colinérgicos/farmacologia , Inositol 1,4,5-Trifosfato/fisiologia , Ratos , Ratos Sprague-Dawley , Receptores de Glutamato Metabotrópico/fisiologia , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologiaRESUMO
Synaptically activated postsynaptic [Ca2+]i increases occur through three main pathways: Ca2+ entry through voltage-gated Ca2+ channels, Ca2+ entry through ligand-gated channels, and Ca2+ release from internal stores. The first two pathways have been studied intensively; release from stores has been the subject of more recent investigations. Ca2+ release from stores in CNS neurons primarily occurs as a result of IP3 mobilized by activation of metabotropic glutamatergic and/or cholingergic receptors coupled to PLC. Ca2+ release is localized near spines in Purkinje cells and occurs as a wave in the primary apical dendrites of pyramidal cells in the hippocampus and cortex. The amplitude of the [Ca2+]i increase can reach several micromolar, significantly larger than the increase due to backpropagating spikes. The large amplitude, long duration, and unique location of the [Ca2+]i increases due to Ca2+ release from stores suggests that these increases can affect specific downstream signaling mechanisms in neurons.
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Cálcio/metabolismo , Sistema Nervoso Central/citologia , Neurônios/metabolismo , Sinapses/metabolismo , AnimaisRESUMO
We investigated the role of A-type K(+) channels for the induction of long-term potentiation (LTP) of Schaffer collateral inputs to hippocampal CA1 pyramidal neurons. When low-amplitude excitatory postsynaptic potentials (EPSPs) were paired with two postsynaptic action potentials in a theta-burst pattern, N-methyl-d-aspartate (NMDA)-receptor-dependent LTP was induced. The amplitudes of the back-propagating action potentials were boosted in the dendrites only when they were coincident with the EPSPs. Mitogen-activated protein kinase (MAPK) inhibitors PD 098059 or U0126 shifted the activation of dendritic K(+) channels to more hyperpolarized potentials, reduced the boosting of dendritic action potentials by EPSPs, and suppressed the induction of LTP. These results support the hypothesis that dendritic K(+) channels and the boosting of back-propagating action potentials contribute to the induction of LTP in CA1 neurons.