只要坚持服“钙神” 可以保证不缺钙

钙是人体骨骼的主要成份。钙是生命之本,人体的神经、循环、呼吸、泌尿、内分泌等系统的一切生命活动都离不开钙。儿童缺钙,可造成生长发育不正常,出现佝偻病、精力不集中、近视;孕妇缺钙,可造成胎儿发育不良、腰酸腿痛、水肿、抽筋、产后“月子病”等;青年人缺钙、可致使腰腿酸痛、疲劳乏力、神经紧张等;中老年人缺钙,可致使骨质疏松、骨质增生、高血压。

神经钙调蛋白介导IL-1β引起的皮层神经元损伤

目的探讨神经钙调蛋白介导IL-1β引起的皮层神经元损伤。方法采用白细胞介素-1β(IL-β)诱导和NMDA诱导原代培养的胎鼠皮层神经元损伤;利用MTT法与LDH释放率测定及观察细胞生存力与损伤程度。结果不同浓度的白细胞介素-1β与NMDA对原代培养的大鼠脑皮质神经损伤具有剂量依赖性;通过乳酸脱氢酶释放率表明,白细胞介素-1β与NMDA均能够诱导神经细胞损伤;白细胞介素-1β与NMDA处理的原代培养大鼠皮层神经元经所发生的细胞凋亡数量与坏死的细胞数量明显多于对照组,差异有统计学意义(P<0.05)。结论神经钙调蛋白参与介导IL-1β引起的神经细胞凋亡,是细胞凋亡信号通路中的重要分子。

Roles of TRESK,a novel two-pore domain K+channel,in pain pathway and general anesthesia

TRESK is the most recently reported two-pore domain K^＋ channel, and different from other two-pore domain channels in gene, molecular structure, electrophysiological and pharmacological properties. Although the current knowledge of this potassium channel is inadequate, researches have demonstrated that TRESK is remarkablely linked to acute and chronic pain by activation of calcineurin. The fact that TRESK is sensitive to volatile anesthetics and localization in central nerve system implies that TRESK may play a very important role in the mechanism mediating general anesthesia. The further research of TRESK may contribute to explore the underlying mechanism of some pathological conditions and yield novel treatments for some diseases.

Mechanisms underlying low [Ca^(2+)]_o-induced increased excitability of hippocampal neurons

Objective Concentration of extracellular calcium （[Ca2＋]o） in the central nervous system decreases substantially in different conditions. It results in facilitating neuronal excitability. The goal of this study is to examine the mechanisms of enhanced neuronal excitation in low [Ca2＋]o in order to provide new clues to treat the hyperexcitability diseases in clinic. Methods Whole-cell patch-clamp technique and neuron culture were used in the study. Results The firing threshold of cultured hippocampal neurons decreased markedly in low [Ca2＋]o saline. Unexpectedly, apamine and isoprenaline, antagonists of medium afterhyperpolarization （mAHP） and slow AHP （sAHP） respectively, had no statistic significant effect on excitability of neurons. TTX at a low concentration was sufficient to inhibit/Nap, which blocked the increase of firing frequency in low [Ca2＋]o. It also reduced the number of spikes in normal [Ca2＋]o. Conclusion These results suggest that in cultured hippocampal neurons, modulation of spiking threshold but not AHP may cause the increased excitability in low [Ca2＋]o.

Effects of Rhynchophylline on L type Calcium Channels in Isolated Rat Cortical Neurons During Acute Hypoxia

Aim: To study the effects of rhynchophylline (Rhy) on the L type calcium channels in freshly dissociated cortical neurons of Wistar rats during acute hypoxia. Methods: Cell attached configuration of patch clamp technique. L type calcium channel was activated by stepping from 40 mV to 0 mV. Results: The results showed that the L type calcium channels of cortical neurons were activated by acute hypoxia. The mean open time of the channel was increased, the mean close time decreased and the open state probability raised during acute hypoxia. Rhy (15 and 30μmol·L -1 ) in concentration dependent manner blocked activity of the channels. The drug shortened the mean open time of the channels from 8 87 ms to 3 03 ms and 2 23 ms ( P 【0 001), prolonged the mean close time from 9 23 ms to 38 84 ms and 54 43 ms ( P 【0 001), and decreased the open state probability from 0 142 to 0 031 and 0 025 ( P 【0 001) under the hypoxia condition, respectively. The effects of Rhy were similar to but weaker than those of verapamil (15 μmol·L -1 ). Conclusion: The study confirmed that Rhy has the blockade effects on L type calcium channels in cortical neurons of rats during hypoxia, by which it protects the brain from hypoxic injury.

CIPK9: a calcium sensor-interacting protein kinase required for low-potassium tolerance in Arabidopsis

Potassium is one of the major macro-nutrients essential for a number of cellular processes in plants. Low potassium level in the soil represents a limiting factor for crop production. Recent studies have identified potassium transporters that are involved in potassium acquisition, and some of them are critical for potassium nutrition under low potassium conditions. However, little is understood on the molecular components involved in low potassium signaling and responses. We report here the identification ofa calcineurin B-like protein-interacting protein kinase （CIPK9） as a critical regulator of low potassium response in ,Arabidopsis. The CIPK9 gene was responsive to abiotic stress conditions, and its transcript was inducible in both roots and shoots by potassium deprivation. Disruption of CIPK9 function rendered the mutant plants hypersensitive to low potassium media. Further analysis indicated that K^＋ uptake and content were not affected in the mutant plants, implying CIPK9 in the regulation of potassium utilization or sensing processes.

Simultaneous Determination of Calcium and Magnesium in Water Using Artificial Neural Network Spectro-Photometric Method

A new analytical method using Back-Propagation （BP） artificial neural networks and spectrophotometry for simultaneous determination of calcium and magnesium in tap water, the Yellow River water and seawater is established. By condition experiment, the optimum analytical conditions for calcium, magnesium and Arsenazo （Ⅲ） color reactions are obtained. Levenberg- Marquart （L-M） algorithm is used for calculation in BP neural network. The topological structure of three-layer BP ANN network architecture is chosen as 11-10-2 （nodes）. The initial value of gradient coefficient μ is fixed at 0.001 and the increase factor and reduction factor of kt take the default values of the system. The data are processed by computers with our own programs written in MATLAB 7.0. The relative standard deviations of the calculated results for calcium and magnesium are 2.31% and 2.14%, respectively. The results of standard addition method show that the recoveries of calcium and magnesium are 103.6% and 100.8% in the tap water, 103.2% and 96.6% in the Yellow River water （Lijin district of Shandong Province）, and 98.8%-103.3% and 98.43%-103.4% in seawater from Jiaozhou Bay of Qingdao. It is found that 14 common cations and anions do not interfere with the determination of calcium and magnesium under the optimum experimental conditions. The comparative experiments do not show any obvious differ- ence between the results obtained by this new method and those obtained by the classical complexometric titration method in seawater medium. This method exhibits good reproducibility and high accuracy in the determination of calcium and magnesium and can be used for the simultaneous determination of Ca^2＋ and Mg^2＋ in tap water and natural water.

ROLE OF CALCINEURIN IN ANGIOTENSIN II- INDUCED CARDIAC MYOCYTE HYPERTROPHY OF RATS

The present study investigated the role of calcineurin in angiotensin II(AngII)- induced cardiac myocyte hypertrophy of rats. Method. The primary cardiac myocytes were cultured under the standard conditions. The calcineurin activity in AngII- treated cardiomyocytes was tested by using PNPP;protein synethsis rate was assessed by 3H- leucine incorporation; atrial natriuretic factor(ANF) mRNA level was determined by Northern blot analysis. Cell viability was estimated by lactate dehydrogenase(LDH) levels in cultured medium and by dyed cell numbers. Result. After stimulation of 10,100 and 1 000nmol/L of AngII, calcineurin activities in the cardiomyocytes were increased by 13％ ,57％ (P Conclusion. During AngII- induced cardiac myocyte hypertrophy, calcineurin signal pathway is activated, and inhibition of the pathway can attenuate AngII- induced cardiac myocyte hypertrophy, which suggests that the calcineurin signal pathway may play an important role in AngII- induced myocardial hypertrophy of rats.

Calcineurin signalling mechanisms in myocardial hypertrophy

Calcineurin dephosphorylates multiple serine residues near the N terminus of NFAT proteins enabling them to translocate from cytoplasm to nucleus, where they activate a subset of hypertrophic response genes. Transgenic mice over-expressing a constitu- tively active form of calcineurin or NFAT3, developed obviously hypertrophy and heart failure or sudden death proving its pathogenic role. Here we used literatures on MEDLINE （2000-2011）, systematically reviewed the new development of calcineurin signaling pathway in myocardial hypertrophy

Role of calcium and magnesium infusion in prevention of oxaliplatin neurotoxicity. A phase III trial

Objective： This study is a prospective randomized, double-blind, placebo-controlled study to evaluate the effect of calcium and magnesium （Ca/Mg） infusion on amelioration of oxaliplatin neuropathy, the dose-limiting toxicity. Methods： Sixty patients with resected colorectal carcinoma （CRC） planned to receive adjuvant oxaliplatin-containing regimen were randomly assigned to two arms; Arm A： patients received Ca/Mg were given as 1 gm Ca gluconate and 1 gm MgSO4 in 250 mL of intravenous （IV） solution over 30 rain pre and post oxaliplatin infusion, and Arm B： patients received 250 mL of IV solution without Ca/Mg over 30 min pre and post oxaliplatin infusion. Primary outcome was to assess percentage of patients with oxaliplatin-induced neurotoxicity. Neurotoxicity was assessed according to the National Cancer Institute Common Terminology Criteria forAdverse Events （NCI-CTCAE） version 3.0. Results： Sixty patients in both arms were assessed, 30 with Ca/Mg infusion and 30 without. Patients developed neurotoxicity in arm A were significantly lower than that in arm B after the end of treatment; 7 （23.3%） and 14 （46.6%） respectively （P 〈 0.05）, and significantly lower duration of neuropathy in months （8 ± 2.5 vs 18 ±3） respectively （P 〈 0.001）. Conclusion： Use of IV Ca/Mg showed a statistically significant reduction of peripheral neuropathy （PN） in patients with CRC receiving oxaliplatin in the adjuvant settings.

Effect of motilin and erythromycin on intracellular Ca2+ mobilization in rat myenteric neurons in culture

Objective: To investigate the effects of motilin and erythromycin on intracellular Ca2+ mobi-lization in cultured myenteric neurons of rats. Methods: The cultured myenteric neurons were identified with immunofluorescence staining technique. Motilin-induced and erythromycin-induced intracellular Ca2+ mobilization was studied in primary cultures of myenteric neurons using the ratiometric Ca2+ indicator Furo3/AM, with a laser confocal microscope. Results: The effects of motilin and erythromycin on intracellular Ca2+ mobilization were as follows: (1)In Hank's solution, 10 -8, 10-7, 10-6 mol/L motilin could elevate intracellular Ca2+ concentration ([Ca2+]i)in a dose-dependent manner. (2) In Hank's solution, 10μg/ ml erythromycin also could induce the elevation of [Ca2+]i. (3) After pretreatment with antibody against the motilin receptor in Hank's solution, the Ca2+ response to erythromycin was almost restricted. Conclusion: It is suggested that motilin could increase [Ca2+]i in myenteric neurons in a dose-dependent manner, and erythromycin may also have this effectivenesss by binding to the motilin receptor.

Functional analysis of calcium channel-mediated exocytosis in synaptic terminals by FM imaging technique

Objective Presynaptic voltage-gated Ca^2＋ channels mediate rapid Ca^2＋ influx into the synaptic terminal which triggers synaptic vesicle exocytosis and neurotransmitter release. The FM 1-43 dye was firstly introduced as a fluorescence probe by Betz and his colleagues in 1992, and has been used to monitor exocytosis, endocytosis and endosomal traffic in a variety of cell types. The present study aims to investigate the feasibility of applying the FM 1-43 dye in the functional analysis of calcium channel-mediated exocytosis in synaptic terminals. Methods The hippocampi were isolated from embryos of pregnant rats, and hippocampal neurons were then transfected with Ds-Red conjugated plasmid. The neurons were then loaded with 8 μmol/L FM 1-43 and 47 mmol/L KCl for 90 s after transfection. After that, 90 mmol/L KCI was employed to induce FM dye destaining, which was recorded by FM imaging system. Results The neuron synaptic terminals of rat hippocampus could be effectively stained by the FM 1-43 dye. Besides, the destaining of the labeled neuron terminals was in accordance with the transmitter release, which could be blocked by the application of nifedipine （inhibitor for L-type calcium channel）. Conclusion The FM imaging technique is an advanced and effective method for analyzing synaptic vesicle exocytosis and neurotransmitter release, and can be applied in various synaptic functional studies.

RGK regulation of voltage-gated calcium channels

Voltage-gated calcium channels(VGCCs) play critical roles in cardiac and skeletal muscle contractions,hormone and neurotransmitter release,as well as slower processes such as cell proliferation,differentiation,migration and death.Mutations in VGCCs lead to numerous cardiac,muscle and neurological disease,and their physiological function is tightly regulated by kinases,phosphatases,G-proteins,calmodulin and many other proteins.Fifteen years ago,RGK proteins were discovered as the most potent endogenous regulators of VGCCs.They are a family of monomeric GTPases(Rad,Rem,Rem2,and Gem/Kir),in the superfamily of Ras GTPases,and they have two known functions: regulation of cytoskeletal dynamics including dendritic arborization and inhibition of VGCCs.Here we review the mechanisms and molecular determinants of RGK-mediated VGCC inhibition,the physiological impact of this inhibition,and recent evidence linking the two known RGK functions.

p38α MAP kinase phosphorylates RCAN1 and regulates its interaction with calcineurin

RCAN1, also known as DSCR1, is an endogenous regulator of calcineurin, a serine/threonine protein phosphatase that plays a critical role in many physiological processes. In this report, we demonstrate that p38a MAP kinase can phosphorylate RCAN1 at multiple sites in vitro and show that phospho-RCAN1 is a good protein substrate for calcineurin. In addition, we found that unphosphorylated RCANI noncompetitively inhibits calcineurin protein phosphatase activity and that the phosphorylation of RCAN1 by p38a MAP kinase decreases the binding affinity of RCAN1 for calcineurin. These findings reveal the molecular mechanism by which p38a MAP kinase regulates the function of RCAN1/calcineurin through phosphorylation.

Astrocyte calcium wave induces seizure-like behavior in neuron network

It has been revealed experimentally that astrocytes can participate in synaptic transmission by modulating and responding to the release of neurotransmitters with calcium elevations. Researches suggest that seizure-like discharges(SDs) or seizure-like firings(SFs) in neurons, characterizing neurological disorder, may arise locally in restricted areas(focal area) and then propagate throughout the brain. But the underlying mechanism remains unclear. To study the possible role astrocytes playing in the SDs propagation, we construct a minimal neuron-astrocyte network model by connecting a neurons chain and an astrocytes chain.The focal area is modelled by an IP3 reservoir which provides persistent IP3 out-flux. The study suggests that calcium wave propagation in astrocytes determines the propagation of SDs in the connected neurons. On the other hand, SDs in neurons allows the calcium wave propagates longer distance in the astrocytes, which suggests the mutually cooperating of astrocytes and neurons in accomplishing SD propagation. Furthermore, once SDs propagate and occupy the neuron network, it could not be terminated by recovery of the focal area. The results may imply that treatment of brain disorders should not only focus on local area but the whole neuron network.

Regulatory effects of insulin-like growth factor-1 on the expression of sensory neuropeptide mRNAs in cultured dorsal root ganglion neurons with excitotoxicity induced by glutamate

Objective To determine the effects of insulin-like growth factor-1 （IGF-1） on the expression of preprotachykinin （PPT） mRNA encoding substance P （SP） and calcitonin gene-related peptide （CGRP） mRNA in cultured dorsal root ganglion （DRG） neurons with excitotoxicity induced by glutamate （Glu）. Methods DRGs were dissected from embryonic day 15 Wistar rats. DRG neurons were dissociated and cultured for 48 h and then exposed to Glu （0.2 mmol/L） or Glu （0.2 mmol/L） plus IGF- 1 （5 nmol/L, 10 nmol/L and 20 nmol/L） for 12 h. The DRG neurons in control group were exposed to only growth media throughout the experiment. After that, the living DRG neurons were observed under inverted phase contrast microscope and microphotographs were taken. The expression levels of PPT and CGRP mRNAs were detected by reverse transcriptionpolymerase chain reaction （RT-PCR）. Results IGF-1 could inhibit Glu-induced shortening of neurite. Besides, IGF-1 could significantly increase the levels ofPPT mRNA and CGRP mRNA in primary cultured DRG neurons with Glu-induced excitotoxicity, in a dose-dependent manner. Conclusion IGF-1 may exert neuroprotective effects on DRG neurons against Glu-induced excitotoxicity, probably through regulating the expression levels of PPT and CGRP mRNAs.

Presenilins as endoplasmic reticulum calcium leak channels and Alzheimer's disease pathogenesis

Alzheimer disease(AD) is the most common neurodegenerative disorder worldwide and is at present,incurable.The accumulation of toxic amyloid-beta(Aβ) peptide aggregates in AD brain is thought to trigger the extensive synaptic loss and neurodegeneration linked to cognitive decline,an idea that underlies the'amyloid hypothesis'of AD etiology in both the familal(FAD) and sporadic forms of the disease.Genetic mutations causing FAD also result in the dysregulation of neuronal calcium(Ca2+) handling and may contribute to AD pathogenesis,an idea termed the'calcium hypothesis'of AD.Mutations in presenilin proteins account for majority of FAD cases.Presenilins function as catalytic subunit ofγ-secretase involved in generation of Aβ peptide Recently,we discovered that presenilns function as low-conductance,passive ER Ca2+ leak channels,independent of γ-secretase activity.We further discovered that many FAD mutations in presenilins result in loss of ER Ca2+ leak function activity and Ca2+ overload in the ER.These results provided potential explanation for abnormal Ca2+ signaling observed in FAD cells with mutations in presenilns.Our latest work on studies of ER Ca2+ leak channel function of presenilins and implications of these findings for understanding AD pathogenesis are discussed in this article.

Early calcium dysregulation in Alzheimer's disease:setting the stage for synaptic dysfunction

Alzheimer's disease(AD) is an irreversible and progressive neurodegenerative disorder with no known cure or clear understanding of the mechanisms involved in the disease process.Amyloid plaques,neurofibrillary tangles and neuronal loss,though characteristic of AD,are late stage markers whose impact on the most devastating aspect of AD,namely memory loss and cognitive deficits,are still unclear.Recent studies demonstrate that structural and functional breakdown of synapses may be the underlying factor in AD-linked cognitive decline.One common element that presents with several features of AD is disrupted neuronal calcium signaling.Increased intracellular calcium levels are functionally linked to presenilin mutations,ApoE4 expression,amyloid plaques,tau tangles and synaptic dysfunction.In this review,we discuss the role of AD-linked calcium signaling alterations in neurons and how this may be linked to synaptic dysfunctions at both early and late stages of the disease.