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101.
102.
Yuanyuan Zheng Limin Wang Zhixiang Zhu Xinxin YanLane Zhang Pingxiang XuDali Luo 《Thrombosis research》2014
Introduction
Downregulation of calsequestrin (CSQ), a major Ca2 + storage protein, may contribute significantly to the hyperactivity of internal Ca2 + ([Ca2 +]i) in diabetic platelets. Here, we investigated changes in CSQ-1 abundance, Ca2 + signaling and aggregation responses to stimulation with the progression of diabetes, especially the mechanism(s) underlying the exaggerated Ca2 + influx in diabetic platelets.Materials and methods
Type 1 diabetes was induced by streptozotocin in rats. Platelet [Ca2 +]i and aggregation responses upon ADP stimulation were assessed by fluorescence spectrophotometry and aggregometry, respectively. CSQ-1 expression was evaluated using western blotting.Results
During the 12-week course of diabetes, the abundance of CSQ-1, basal [Ca2 +]i and ADP-induced Ca2 + release were progressively altered in diabetic platelets, while the elevated Ca2 + influx and platelet aggregation were not correlated with diabetes development. 2-Aminoethoxydiphenyl borate, the store-operated Ca2 + channel blocker, almost completely abolished ADP-induced Ca2 + influx in normal and diabetic platelets, whereas nifedipine, an inhibitor of the nicotinic acid adenine dinucleotide phosphate receptor, showed no effect. Additionally, inhibition of Na+/Ca2 + exchange induced much slower Ca2 + extrusion and more Ca2 + influx in normal platelets than in diabetic platelets. Furthermore, under the condition of Ca2 +-ATPase inhibition, ionomycin caused greater Ca2 + mobilization and Ca2 + influx in diabetic platelets than in normal platelets.Conclusions
These data demonstrate that platelet hyperactivity in diabetes is caused by several integrated factors. Besides the downregulation of CSQ-1 that mainly disrupts basal Ca2 + homeostasis, insufficient Na+/Ca2 + exchange also contributes, at least in part, to the hyperactive Ca2 + response to stimulation in diabetic platelets. 相似文献103.
Stefanie Ryglewski Lukas Kilo Carsten Duch 《The European journal of neuroscience》2014,39(10):1572-1585
During metamorphosis the CNS undergoes profound changes to accommodate the switch from larval to adult behaviors. In Drosophila and other holometabolous insects, adult neurons differentiate either from respecified larval neurons, newly born neurons, or are born embryonically but remain developmentally arrested until differentiation during pupal life. This study addresses the latter in the identified Drosophila flight motoneuron 5. In situ patch‐clamp recordings, intracellular dye fills and immunocytochemistry address the interplay between dendritic shape, excitability and ionic current development. During pupal life, changes in excitability and spike shape correspond to a stereotyped, progressive appearance of voltage‐gated ion channels. High‐voltage‐activated calcium current is the first current to appear at pupal stage P4, prior to the onset of dendrite growth. This is followed by voltage‐gated sodium as well as transient potassium channel expression, when first dendrites grow, and sodium‐dependent action potentials can be evoked by somatic current injection. Sustained potassium current appears later than transient potassium current. During the early stages of rapid dendritic growth, sodium‐dependent action potentials are broadened by a calcium component. Narrowing of spike shape coincides with sequential increases in transient and sustained potassium currents during stages when dendritic growth ceases. Targeted RNAi knockdown of pupal calcium current significantly reduces dendritic growth. These data indicate that the stereotyped sequential acquisition of different voltage‐gated ion channels affects spike shape and excitability such that activity‐dependent calcium influx serves as a partner of genetic programs during critical stages of motoneuron dendrite growth. 相似文献
104.
Cell type–specific spatial and functional coupling between mammalian brain Kv2.1 K+ channels and ryanodine receptors 下载免费PDF全文
Danielle Mandikian Elke Bocksteins Laxmi Kumar Parajuli Hannah I. Bishop Oscar Cerda Ryuichi Shigemoto James S. Trimmer 《The Journal of comparative neurology》2014,522(15):3555-3574
The Kv2.1 voltage‐gated K+ channel is widely expressed throughout mammalian brain, where it contributes to dynamic activity‐dependent regulation of intrinsic neuronal excitability. Here we show that somatic plasma membrane Kv2.1 clusters are juxtaposed to clusters of intracellular ryanodine receptor (RyR) Ca2+‐release channels in mouse brain neurons, most prominently in medium spiny neurons (MSNs) of the striatum. Electron microscopy–immunogold labeling shows that in MSNs, plasma membrane Kv2.1 clusters are adjacent to subsurface cisternae, placing Kv2.1 in close proximity to sites of RyR‐mediated Ca2+ release. Immunofluorescence labeling in transgenic mice expressing green fluorescent protein in specific MSN populations reveals the most prominent juxtaposed Kv2.1:RyR clusters in indirect pathway MSNs. Kv2.1 in both direct and indirect pathway MSNs exhibits markedly lower levels of labeling with phosphospecific antibodies directed against the S453, S563, and S603 phosphorylation site compared with levels observed in neocortical neurons, although labeling for Kv2.1 phosphorylation at S563 was significantly lower in indirect pathway MSNs compared with those in the direct pathway. Finally, acute stimulation of RyRs in heterologous cells causes a rapid hyperpolarizing shift in the voltage dependence of activation of Kv2.1, typical of Ca2+/calcineurin‐dependent Kv2.1 dephosphorylation. Together, these studies reveal that striatal MSNs are distinct in their expression of clustered Kv2.1 at plasma membrane sites juxtaposed to intracellular RyRs, as well as in Kv2.1 phosphorylation state. Differences in Kv2.1 expression and phosphorylation between MSNs in direct and indirect pathways provide a cell‐ and circuit‐specific mechanism for coupling intracellular Ca2+ release to phosphorylation‐dependent regulation of Kv2.1 to dynamically impact intrinsic excitability. J. Comp. Neurol. 522:3555–3574, 2014. © 2014 Wiley Periodicals, Inc. 相似文献
105.
Neuroendocrine tuberoinfundibular dopamine (TIDA) neurons tonically inhibit pituitary release of the hormone, prolactin. Through the powerful actions of prolactin in promoting lactation and maternal behaviour while suppressing sexual drive and fertility, TIDA neurons play a key role in reproduction. We summarize insights from recent in vitro studies into the membrane properties and network behaviour of TIDA neurons including the observations that TIDA neurons exhibit a robust oscillation that is synchronized between cells and depends on intact gap junction communication. Comparisons are made with phasic firing patterns in other neuronal populations. Modulators involved in the control of lactation – including serotonin, thyrotropin-releasing hormone and prolactin itself – have been shown to change the electrical behaviour of TIDA cells. We propose that TIDA discharge mode may play a central role in tuning the amount of dopamine delivered to the pituitary and hence circulating prolactin concentrations in different reproductive states and pathological conditions. 相似文献
106.
Introduction: We investigated the clinical, electrophysiological and neural autoantibody characteristics in cramp‐fasciculation syndrome (CFS) patients. Methods: We reviewed Mayo Clinic records from 2000 to 2011 to identify clinically defined CFS patients who underwent neural autoantibody testing. Stored sera of patients who tested positive for antibodies to voltage‐gated potassium channel complex (VGKC complex) were analyzed further for leucine‐rich glioma‐inactivated 1 (LGI1) or contactin‐associated protein‐2 immunoglobulin G (CASPR2‐IgG) antibodies. Results: Thirty‐seven patients were identified. Twelve were seropositive for neural autoantibodies. Clinical manifestations were similar in seropositive and seronegative patients, although central and autonomic neuronal hyperexcitability symptoms were more common in seropositive cases. No patients had a malignancy. Repetitive tibial nerve stimulation at 10 Hz revealed longer afterdischarges in seropositive patients. Two of 7 patients with VGKC‐complex autoimmunity demonstrated LGI1 or CASPR2‐IgG antibodies. Only 2 of 12 seropositive patients required immunotherapy. Conclusions: VGKC‐complex autoimmunity occurs in a minority of CFS patients. Antibody positivity was associated with extramuscular manifestations, typically without malignancy. Target antigens within the VGKC complex remain unknown in most patients. Muscle Nerve 49 :351–356, 2014 相似文献
107.
108.
《Anaesthesia and Intensive Care Medicine》2014,15(10):465-469
Phaeochromocytomas are catecholamine-secreting neuroendocrine tumours arising from the chromaffin cells in the adrenal medulla. These tumours may be identified incidentally, as part of a workup for multiple endocrine neoplasia or during unrelated surgery. Better understanding of catecholamine physiology and advances in preoperative preparation has significantly reduced surgical mortality from around 40% to less than 3%. Surgery is the definitive treatment in most cases and laparoscopic resection is associated with reduced hospital stay and earlier mobilisation. Phaeochromocytomas are of particular interest to anaesthetists as it presents a unique haemodynamic challenge both before and after adrenal resection. In this article we describe the physiology of these tumours, their diagnosis and perioperative management. 相似文献
109.
目的探讨超声辐照参数对体外基因转染效果的影响及最佳转染条件。方法将293T细胞种植于24孔板内,24h后更换为转染液进行超声辐照,EGFP质粒浓度为1mg/ml,每孔加入15μg;超声强度分为1.5、2.0、2.5W/cm2,辐照时间分为30、45、60s,微泡浓度分为20%、30%、40%;每个参数相互组合并重复4次。转染后72h于荧光显微镜下观察细胞内绿色荧光蛋白的表达,以流式细胞仪检测荧光细胞比例,CCK-8检测细胞存活率,计算转染效率。结果超声声强、辐照时间、微泡浓度均对转染效率有显著影响。辐照条件为2.0 W/cm2、辐照时间45s、微泡浓30%时转染效率最高,可达(35.25±1.40)%。结论超声辐照参数共同影响转染效果,低条件下相互协同,高条件下相互抑制,选择合适的辐照参数是超声介导体外基因转染的重要因素。 相似文献
110.
背景 冷过敏是炎性痛和神经病理性疼痛的一个常见症状,其内在机制尚不清楚. 目的 阐明瞬时受体电位通道A1 (transient receptor potential cation channel,subfamily A,member 1,TRPA1)和瞬时受体电位通道M8(transient receptor potential melastatin 8,TRPM8)参与冷过敏的机制. 内容 综述TRPA1和TRPM8的分子结构和门控机制及其在有害的冷、炎性痛和神经病理性疼痛的冷过敏形成、维持中的作用等方面的研究. 趋向 深入研究TRPA1和TRPM8在冷过敏发生中的作用,有助于阐明冷过敏的机制,并为开发拮抗剂提供理论依据. 相似文献