Inhibitory Effects of Blockage of Intermediate Conductance Ca^(2+) -Activated K^+ Channels on Proliferation of Hepatocellular Carcinoma Cells

The roles of intermediate conductance Ca2＋-activated K＋ channel （IKCal） in the pathogene- sis of hepatocellular carcinoma （HCC） were investigated. Immunohistochemistry and Western blotting were used to detect the expression of IKCal protein in 50 HCC and 20 para-carcinoma tissue samples. Real-time PCR was used to detect the transcription level of IKCal mRNA in 13 HCC and 11 para-carcinoma tissue samples. The MTT assay was used to measure the function of IKCal in human HCC cell line HepG2 in vitro. TRAM-34, a specific blocker of IKCal, was used to intervene with the function of IKCal. As compared with para-carcinoma tissue, an over-expression of IKCal protein was detected in HCC tissue samples （P〈0.05）. The mRNA expression level of IKCal in HCC tissues was 2.17 times higher than that in para-carcinoma tissues. The proliferation of HepG2 cells was suppressed by TRAM-34 （0.5, 1.0, 2.0 and 4.0 pxnol/L） in vitro （P〈0.05）. Our results suggested that IKCal may play a role in the proliferation of human HCC, and IKCal blockers may represent a potential therapeutic strategy for HCC.

Changes of Ca^2+ activated potassium channels and cellular proliferation in autogenous vein grafts

Objective: To investigate changes of Ca2+ activated potassium channels (KCa) in autogenous vein grafts. Methods: Contraction of venous ring was measured by means of perfusion in vitro. The intimal rabbits proliferation of vascular and proliferation of cultured smooth muscle cells(vascular smooth muscle cells, VSMCs)were observed by the means of computerised image analysis and MTT method respectively. Furthermore, whole cell mode of patch clamp was used to record KCa of VSMCs isolated from autogenous vein grafts. Results: One week after transplantation there were no significant differences of contraction and intimal relative thickness between autogenous vein grafts and control. Contraction and intimal relative thickness of autogenous vein graft were significantly increased 2 weeks after transplantation (P<0.05, n=8 vs control), and they was more enhanced 4 weeks after vein transplantation (P<0.01, n=8 vs control).TEA(blocker of Ca2+ activated potassium channels)increased MTT A490 nm value of VSMCs from femoral vein in a dose dependent manner(P<0.05, n=8). KCa current density was significantly attenuated in VSMCs from autogenous vein grafts (1-4) week after transplantation(P<0.05, n=5).Conclusion: KCa is inhibited in autogenous vein graft, which account for vasospasm and intimal proliferation.

Effects of isoflurane and ethanol on large conductance Ca^(2+)-activated K^+ channels

Objective: To study the effect of isoflurane and ethanol on large conductance Ca 2+-activated K + channels(BK channels). Methods: The cRNA of mslo1 encoding BK channels was injected into Xenopus oocytes. Oocytes were incubated in ND96 (96 mmol/L NaCl, 2.0 mmol/L KCl, 1.8 mmol/L CaCl 2, 1.0 mmol/L MgCl 2, and 5.0 mmol/L HEPES, pH 7.4) at 4 ℃. Patch clamp recording (outside-out) were performed after 2-3 d. Isoflurane was administrated by the vaporizer driven by air, ethanol was applied by a closed, manual-controlled administration system. Different test potentials from 0 to 10 mV were given to observe changes of currents. Results: 0.7 mmol/L and 1.2 mmol/L of isoflurane could inhibit BK currents obviously at different command potentials, but 50 mmol/L, 100 mmol/L, or 200 mmol/L of ethanol had no any effect on BK currents. Conclusion: Clinical concentration of isoflurane can distinctly inhibit isolating BK currents.

Delivery of CatSper2 siRNA into Rat Sperms by Electroporation Repressed Ca^(2+) Influx During Sperm Hyperactivation

CatSper is a unique Ca2＋ channel-like protein family exclusively expressed in the testis and sperm, and plays important roles in sperm motility, capacitation, acrosome reaction and sperm-egg interactions. Here we studied the mechanism of regulation of CatSper2-dependent Ca〉 influx, extracellular and intracellular Ca2＋on sperm hyperactivated motility. The siRNA duplexes were transfected into the sperm cells by electroporation （EP） to silence the expression of CatSper2. The results for targeted disruption of CatSper2 showed the highest silence efficiency 77.7% （P〈0.05）, the hyperactivated sperm rate calculated by computer-assisted semen analysis （CASA） analysis of interferenced sperm was significantly lower 11.1% than the control 99.2%. Flow cytometry （FCM） detection of the intracellular Ca2＋ concentration of interferenced sperm was 50 nmol L-t higher than the normal. It was remarkably lower than hyperactivated sperm with 200-1 000 nmol L-1 （P〈0.05）. It was not sufficient to evoke hyperactivation. To trigger hyperactivation, the sperm were incubated in 50 pmol L-t thimerosal or 5 mmol L-1 procaine, it sharply increased the intracellular Ca2＋ via two different channels. CASA and FCM detection indicated that intracellular Ca〉 is required for initiating hyperactivation while extracellular Ca2＋ is essential to maintain the process. We concluded that to mediate sperm hyperactivation, it is essential to inhibit Ca〉peak present with targeted disruption of CatSper2 expression. This provides important prospective for further exploration of signal channel of sperm hyperactivated motility, potential factors for male infertility and provide further reference to the exploration of male contraceptive drug targets of male reproduction.

EFFECT OF ELECTROACUPUNCTURE AND CALCIUM-CHANNEL INHIBITORS ON CYTOPLASMIC FREE CALCIUM CONCENTRATION OF MOUSE BRAIN CELLS

Objective: To study the effect of electroacupuncture (EA) and Verapamil and Nifedipine (calcium channel inhibitors) on free calcium concentrations of cells and intrasynaptosomes in hypothalamus (HT), periaqueductual grey matter (PAG) and hippocampus (HIP) of mice. Methods: The female ICR mice were randomly divided into control, EA, CaCl2 and CaCl2+EA groups (n=8 in each group). Pain threshold was detected by using radiation-heat irradiation-induced tail flick method. EA (8 Hz, a suitable stimulating strength, dense-sparse waves and duration of 30 min) was applied to“Shuigou” (水沟 GV 26) and “Chengjiang” (承浆CV 24). CaCl2 (10 μL, 0.2 μmol/L) was injected into the lateral cerebral ventricle of mice after EA. The concentrations of cytosolic free calcium ([Ca 2+]i) in HIP, PAG, HT cell suspension specimen and hippocampal intrasynaptosome suspension of mice were determined by the fluorescent calcium indicator Fura-2-AM and a spectrofluorometer. Results: During EA analgesia, the intracellular free [Ca 2+]i in HT and PAG specimens and intrsynaptosomal [Ca 2+]i of the 3 cerebral regions decreased considerably (P<0.05～0.01), but that in hippocampal cell suspension increased significantly (P<0.01) in comparison with control group. The concentrations of hippocampal intrasynaptosomal free [Ca 2+]i decreased significantly after adding Verapamil and Nifedipine to the extracted hippocampal intrasynaptosomal specimen. Microinjection of CaCl2 into lateral ventricle had no apparent influence on degree of analgesia (DA)% and intracellular and intrasynapsotomal [Ca 2+]i, but significantly lower DA% and reduce changes of cytosolic and intrasynaptosomal [Ca 2+]i induced by EA stimulation. Conclusion: Calcium ion in the neurons and intrasynaptosome of HT, PAG and HIP is involved in electroacupuncture analgesia.

Pharmacological basis for the medicinal use of Michelia champaca in gut, airways and cardiovascular disorders

Objective: To discover the mechanism behind ameliorative effects of Michelia champaca(M. champaca) in gastrointestinal, respiratory and cardiovascular disorders. Methods: Antispasmodic potential was evaluated by trying the M. champaca extract(aqueous:ethanolic) on rabbit aorta, trachea and jejunum in vitro. Isotonic and isometric transducers coupled with Power Lab data acquisition system was used to record the responses of isolated tissues. Results: M. champaca extract relaxed the spontaneous and high K^+(80 mmol/L)-induced contractions of isolated jejunum preparation of rabbit showing a Ca^(2+) channel blocking mechanism. Moreover, extract shifted calcium concentration response curves towards right like standard calcium channel blocker verapamil. In rabbit tracheal preparation, M. champaca relaxed both carbachol(1 μmol/L) and high K^+-induced contractions, likewise verapamil. In rabbit aorta preparation, M. champaca relaxed phenylephrine(1 μmol/L) and high K^+-induced contractions similar to verapamil. Conclusion: M. champaca possesses spasmolytic, airways relaxant and vasodilator actions mediated perhaps due to blocking of Ca^(2+) channels, hence validating its therapeutic usage in diarrhea, asthma and hypertension.

An inherent acceleratory effect of insulin on small intestinal transit and its pharmacological characterization in normal mice

AIM： To study an inherent effect of insulin on small intestinal transit and to explore involvement of various systems/mechanisms in normal mice. METHODS： Insulin at the doses of 2 μU/kg, 2 mU/kg, 2 U/kg or vehicle was subcutaneously administered to four groups of overnight fasted normal male mice. Blood glucose （BG） levels were measured 2 min before insulin administration and 2 min before sacrificing the animals for the measurement of small intestinal transit （SIT）. Charcoal meal was administered （0.3 mL） intragastrically 20 min after insulin administration and animals were sacrificed after 20 min and SIT was determined. For exploration of the various mechanisms involved in insulin-induced effect on SIT, the dose of insulin which can produce a significant acceleration of SIT without altering BG levels was determined. The following drugs, atropine （1 mg/kg）, clonidine （0.1 mg/kg）, ondansetron （1 mg/kg）, naloxone （5 mg/kg）, verapamil （8 mg/kg） and glibenclamide （10 mg/kg）, were administered intravenously 10 min prior to the administration of insulin （2 μU/kg）. RESULTS： The lower doses of insulin （2 μU/kg and 2 mU/kg） produced a significant acceleration of SIT from 52.0% to 70.7% and 73.5% without lowering blood glucose levels （P〈0.01）, while the highest dose of insulin （2 U/kg） produced a fall in blood glucose levels which was also associated with significant acceleration of SIT （P〈0.01）. After pretreatment of insulin （2 μU/kg） group with atropine, insulin could reverse 50% of the inhibition produced by atropine. In clonidine-pretreated group, insulin administration could reverse only 37% of the inhibition produced by clonidine and inhibition of SIT was significant compared with vehicle ＋ insulintreated group, i.e. from 74.7% to 27.7% （P〈0.01）. In ondansetron-pretreated group, insulin administration could produce only mild acceleration of SIT （23.5%）. In naloxone-pretreated group, insulin administration could significantly reverse the inhibition of SIT produced by naloxone when compared with naloxoneperse group, i.e. from 32.3% to 53.9% （P〈0.01）. In verapamil-pretreated group, insulin administration could only partially reverse the inhibition （65%）. In glibenclamide-pretreated group, insulin administration produced further acceleration of SIT （12.2%）. CONCLUSION： Insulin inherently possesses an acceleratory effect on SIT in normal mice. Adrenergic and cholinergic systems can play a significant role. Calcium channels and opioidergic system can play a supportive role; in addition, enhancement of endogenous insulin release can augment the effect of exogenously administered insulin on SIT.

THE ROLE OF CALCIUM ION IN THE PATHOGENESIS OF HUMAN PITUITARY GH－SECRETING ADENOMAS

To study the role of Ca2+ in the pathogenesis of pituitary growth hormone secreting adenomas, the function of Ca2+ in 23 cases of human Prturtary GH-secreting adenoma was investigated in monolayer cell culture. It was found that Ca2+ channel blockers nicardipin and nifedipin inhibrted basal and growth hormone releasing hormone (GRH)stimulated GH secretion in 87. 5 % and 100. 0 % of the GH adenomas . respectively, demonstrating that in most human pituitary GH adenomas, the basal and GRH regulated GH secretion is Ca2+ dependent. The GRH and sometostatin (SRIF) agonist octreotide regulated the processes of GH secretion via Ca2+ had defects in different steps including receptor ,postreceptor Ca2+ channel and Ca2+GH secreting coupling in 6 (66. 6%) and 5 (55. 5 % ) cases of 9 GH adenomas respectively. Among them,the defects in GRH receptor and SRIF regulated Ca2+ channel are the main causes of the dysfunction of GH adenomas. These defects may be related to GH hypersecretion in GH adenomas. Our data provides advance evidences for intrinsic defects of GH adenomas.

Effect of Calmodulin and Voltage-dependent Ca^(2+) Channel on the Proliferation of Heptoma Cells Induced by Epidermal Growth Factor

The effect of thyrosine kinase, calmodulin and voltage-dependent Ca 2+ channel on the proliferation of hepatoma cells induced by EGF was studied. Hepatoma cell line SMMC7721 was cultured in RPMI1640 serum-free medium. DNA synthesis rate of hepatoma cells was measured by 3H-TdR incorporation. 10 -9 mol/L EGF could significantly stimulate the proliferation of hepatoma cells (P<0.05), and this effect might be significantly inhibited by tyrosine kinase inhibitor (P<0.001). Calmodulin inhibitor W-7 had no effect on the basic phase of cultured hepatoma cells (P> 0.05), but it had very significantly inhibitory effect on the proliferation of hepatoma cells induced by EGF (P<0.001). Voltage-dependent Ca 2+ channel inhibitor Varapamil had no inhibition on the proliferation of hepatoma cells induced by EGF (P>0.05). It had no effect on the basic phase of cultured hepatoma cells (P>0.05). It is suggested that tyrosine kinase and Ca 2+-calmodulin-dependent pathway may play a critical role on the proliferation of heptoma cells induced by EGF, and voltage-dependent Ca 2+ channel is independent of the effect of EGF.

EPICS控制系统中的Oracle数据库采集

介绍EPICS(Experimental physics and industrial control system)控制系统中针对Oracle的数据库采集。深入剖析了EPICS通讯协议、Oracle联网协议,详细介绍了采集软件的体系结构和实现方法,最后对EPICS 稳定性做了测试。本文给出了采集程序对控制系统影响的测试结果和采集程序运行情况。

Effect of rhubarb on contractile response of gallbladder smooth muscle strips isolated from guinea pigs

AIM: To investigate the effect of rhubarb on contractile response of isolated gallbladder muscle strips from guinea pigs and its mechanism.METHODS: Guinea pigs were killed to remove the whole gallbladder. Two or three smooth muscle strips (8 mm×3mm) were cut along the longitudinal direction. The mucosa on each strip was carefully removed. Each longitudinal muscle strip was suspended in a tissue chamber containing 5 mL Krebs solution (37 ℃), bubbled continuously with 950 mL/L O2 and 50 mL/L CO2. The resting tension (g), mean contractile amplitude (mm),and contractile frequency (waves/min) were simultaneously recorded on recorders. After 2-h equilibration, rhubarb (10, 20, 70, 200, 700, 1 000 g/L) was added cumulatively to the tissue chamber in turns every 2 min to observe their effects on gallbladder.Antagonists were given 3 min before administration of rhubarb to investigate the possible mechanism.RESULTS: Rhubarb increased the resting tension (from 0 to 0.40±0.02, P＜0.001), and decreased the mean contractile amplitude (from 5.22±0.71 to 2.73±0.41,P＜0.001). It also increased the contractile frequency of the gallbladder muscle strips in guinea pigs (from 4.09±0.46to 6.08±0.35, P＜0.001). The stimulation of rhubarb on the resting tension decreased from 3.98±0.22 to 1.58±0.12by atropine (P＜0.001), from3.98±0.22 to 2.09±0.19 by verapamil (P＜0.001) and from 3.98±0.22 to 2.67±0.43by phentolamine (P＜0.005). But the effect was not inhibited by hexamethonium (P＞0.05). In addition, the action of mean amplitude and frequency was not inhibited by the above antagonists.CONCLUSION: Rhubarb can stimulate the motility of isolated gallbladder muscle strips from guinea pigs. The stimulation of rhubarb might be relevant with M receptor,Ca2+ channel and α receptor partly.

HEF-19-induced relaxation of colonic smooth muscles and the underlying mechanisms

AIM:To investigate the relaxant effect of chromane HEF-19 on colonic smooth muscles isolated from rabbits,and the underlying mechanisms.METHODS:The relaxant effect and action mechanisms of HEF-19 were investigated using descending colon smooth muscle of the rabbits.Preparations 1 cm long were mounted in 15-mL tissue baths containing Tyrode’s solution,maintained at 37±0.5℃and aerated with a mixture of 5%CO2in oxygen(Carbogen).The tension and amplitude of the smooth muscle strips were recorded after adding HEF-19(10-6,10-5and 10-4mol/L).After cumulative administration of four antispasmodic agents,including acetylcholine chloride(Ach)(10-4mol/L),histamine(10-4mol/L),high-K+(60 mmol/L)and BaCl2(8.2 mmol/L),HEF-19(3×10-7-3×10-4mol/L)was added to investigate the relaxant effect of HEF-19.CaCl2(10-4-2.5×10-3mol/L)was added cumulatively to the smooth muscle preparations pretreated with and without HEF-19(1×10-6or 3×10-6mol/L)and verapamil(1×10-7mol/L)to study the mechanisms involved.Finally,phasic contraction was induced with ACh(15×10-6mol/L),and CaCl2(4×10-3mol/L)was added to the smooth muscle preparations pretreated with and without HEF-19(3×10-6mol/L or 1×10-5mol/L)and verapamil(1×10-7mol/L)in calcium-free medium to further study the underlying mechanisms.RESULTS:HEF-19(1×10-6,1×10-5and 1×10-4mol/L)suppressed spontaneous contraction of rabbit colonic smooth muscles.HEF-19(3×10-7-3×10-4mol/L)relaxed in a concentration-dependent manner colonic smooth muscle preparations pre-contracted with BaCl2,high-K+solution,Ach or histamine with respective EC50values of 5.15±0.05,5.12±0.08,5.58±0.16and 5.25±0.24,thus showing a spasmolytic activity.HEF-19(1×10-6mol/L and 3×10-6mol/L)shifted the concentration-response curves of CaCl2to the right and depressed the maximum response to CaCl2.The two components contracted by Ach were attenuated with HEF-19(3×10-6mol/L or 10-5mol/L)in calcium-free medium.CONCLUSION:HEF-19 inhibited rabbit colonic smooth muscle contraction,probably through inhibiting opening of voltage-dependent Ca2+channels.HEF-19 reduced inflow and intracellular release of Ca2+ions.

Three CNGC Family Members, CNGC5, CNGC6, and CNGC9, Are Required for Constitutive Growth of Arabidopsis Root Hairs as Ca2+-Permeable Channels

The genetic identities of Ca2+ channels in root hair (RH) tips essential for constitutive RH growth have remained elusive for decades. Here, we report the identification and characterization of three cyclicnucleotide-gated channel (CNGC) family members, CNGC5, CNGC6, and CNGC9, as Ca2+ channels essential for constitutive RH growth in Arabidopsis. We found that the cngc5-1cngc6-2cngc9-1 triple mutant(designated shrh1) showed significantly shorter and branching RH phenotypes as compared with thewild type. The defective RH growth phenotype of shrh1 could be rescued by either the expression ofCNGC5, CNGC6, or CNGC9 single gene or by the supply of high external Ca2+, but could not be rescuedby external K+ supply. Cytosolic Ca2+ imaging and patch-clamp data in HEK293T cells showed that thesethree CNGCs all function as Ca2+-permeable channels. Cytosolic Ca2+ imaging in growing RHs furthershowed that the Ca2+ gradients and their oscillation in RH tips were dramatically attenuated in shrh1compared with those in the wild type. Phenotypic analysis revealed that these three CNGCs are Ca2+ channels essential for constitutive RH growth, with different roles in RHs from the conditional player CNGC14.Moreover, we found that these three CNGCs are involved in auxin signaling in RHs. Taken together, ourstudy identified CNGC5, CNGC6, and CNGC9 as three key Ca2+ channels essential for constitutive RHgrowth and auxin signaling in Arabidopsis.

Structure, biochemical function, and signaling mechanism of plant NLRs

To counter pathogen invasion,plants have evolved a large number of immune receptors,including membrane-resident pattern recognition receptors(PRRs)and intracellular nucleotide-binding and leucine-rich repeat receptors(NLRs).Our knowledge about PRR and NLR signaling mechanisms has expanded significantly over the past few years.Plant NLRs form multi-protein complexes called resistosomes in response to pathogen effectors,and the signaling mediated by NLR resistosomes converges on Ca2+-permeable channels.Ca2+-permeable channels important for PRR signaling have also been identified.These findings highlight a crucial role of Ca2+in triggering plant immune signaling.In this review,we first discuss the structural and biochemical mechanisms of non-canonical NLR Ca2+channels and then summarize our knowledge about immune-related Ca2+-permeable channels and their roles in PRR and NLR signaling.We also discuss the potential role of Ca2+in the intricate interaction between PRR and NLR signaling.

Targeting calcium signaling in cancer therapy

The intracellular calcium ions(Ca^(2+)) act as second messenger to regulate gene transcription,cell proliferation, migration and death. Accumulating evidences have demonstrated that intracellular Ca^(2+)homeostasis is altered in cancer cells and the alteration is involved in tumor initiation, angiogenesis,progression and metastasis. Targeting derailed Ca^(2+)signaling for cancer therapy has become an emerging research area. This review summarizes some important Ca^(2+)channels, transporters and Ca^(2+)-ATPases,which have been reported to be altered in human cancer patients. It discusses the current research effort toward evaluation of the blockers, inhibitors or regulators for Ca^(2+)channels/transporters or Ca^(2+)-ATPase pumps as anti-cancer drugs. This review is also aimed to stimulate interest in, and support for researchinto the understanding of cellular mechanisms underlying the regulation of Ca^(2+)signaling in different cancer cells, and to search for novel therapies to cure these malignancies by targeting Ca^(2+)channels or transporters.

Molecular mechanisms of diabetic coronary dysfunction due to large conductance Ca2＋-activated K＋ channel impairment

Background Diabetes mellitus is associated with coronary dysfunction, contributing to a 2- to 4-fold increase in the risk of coronary heart diseases. The mechanisms by which diabetes induces vasculopathy involve endothelial-dependent and -independent vascular dysfunction in both type 1 and type 2 diabetes mellitus. The purpose of this study is to determine the role of vascular large conductance Ca2＋-activated K＋ （BK） channel activities in coronary dysfunction in streptozotocin-induced diabetic rats. Methods Using videomicroscopy, immunoblotting, fluorescent assay and patch clamp techniques, we investigated the coronary BK channel activities and BK channel-mediated coronary vasoreactivity in streptozotocin-induced diabetic rats. Results BK currents （defined as the iberiotoxin-sensitive K＋ component） contribute （65＋4）% of the total K＋currents in freshly isolated coronary smooth muscle cells and 〉50% of the contraction of the inner diameter of coronary arteries from normal rats. However, BK current density is remarkably reduced in coronary smooth muscle cells of streptozotocin-induced diabetic rats, leading to an increase in coronary artery tension. BK channel activity in response to free Ca2＋ iS impaired in diabetic rats. Moreover, cytoplasmic application of DHS-1 （a specific BK channel i~ subunit activator） robustly enhanced the open probability of BK channels in coronary smooth muscle cells of normal rats. In diabetic rats, the DHS-1 effect was diminished in the presence of 200 nmol/L Ca2＋ and was significantly attenuated in the presence of high free calcium concentration, i.e., 1 μmol/L Ca2＋. Immunoblotting experiments confirmed that there was a 2-fold decrease in BK-β1 protein expression in diabetic vessels, without alterinq the BK channel a-subunit expression.Although the cytosolic Ca2＋ concentration of coronary arterial smooth muscle cells was increased from （103±23） nmol/L （n=5） of control rats to （193±22） nmol/L （n=6, P 〈0.05） of STZ-induced diabetic rats, reduced BK-β1 expression made these channels less sensitive to intracellular Ca2＋, which in turn led to enhanced smooth muscle contraction. Conclusions Our results indicated that BK channels are the key determinant of coronary arterial tone. Impaired BK channel function in diabetes mellitus is associated with down-regulation of BK-β1 expression and reduction of the β1-mediated BK channel activation in diabetic vessels.

Modeling the mechanics of calcium regulation in T lymphocyte:A finite element method approach

Changes in cellular Ca2+concentration control a variety of physiological activities including hormone and neurotransmitter release,muscular contraction,synaptic plas-ticity,ionic channel permeability,apoptosis,enzyme activity,gene transcription and reproduction process.Spatial-temporal Ca2+dynamics due to Ca2 t release,buffering and re-uptaking plays a central role in studying the Ca2+regulation in T lympho-cytes.In most cases,Ca2+has its major signaling function when it is elevated in the cytosolic compartment.In this paper,a two-dimensional mathematical model to study spatiotemporal variations of intracellular Ca2+concentration in T lymphocyte cell is proposed and investigated.The cell is assumed to be a circular shaped geomnetrical domain for the representation of properties of Ca2+dynamics within the cell includ-ing important parameters.Ca2+binding proteins for the dynamics of Ca2+are itself buffer and other physiological parameters located in Ca2+stores.The model incorpo-rates the important biophysical processes like difusion,reaction,voltage gated Ca2+channel,leak from endoplasmic reticulum(ER),efflux from cytosol to ER via sarco ER Ca2+adenosine triphosphate(SERCA)pumps,buffers and Na+/Ca2+exchanger.The proposed mathematical model is solved using a finite difference method and the finite element method.Appropriate initial and boundary conditions are incorporated in the model based on biophysical conditions of the problem.Computer simulations in MAT-LAB R2019b are employed to investigate mathematical models of reaction-diffusion equation.The effect of source,buffer,Nat/Ca2+exchanger,etc.on spatial and tempo-ral patterns of Ca2+in T lymphocyte has been studied with the help of numerical results.From the obtained results,it is observed that,the coordinated combination of the incor-porated parameters plays a significant role in Ca2+regulation in T lymphocytes.ER leak and voltage-gated Ca2+channel provides the necessary Ca2+to the cell when required for its proper functioning,while on the other side buffers,SERCA pump and Na+/Ca2+exchanger makes balance in the Ca2+concentration,so as to prevent the cell from death as higher concentration for longer time is harmful for the cell and can cause cell death.

Contribution of L-type Ca^(2+) channel to the regulation of coronary arterial smooth muscle contraction is different in rats and mice

Background L-type calcium channel participates in the regulation of a variety of physical and pathological process. In vasculature, it mainly mediated agonist-induced vascular smooth muscle contraction. However, it is not clear whether there are differences in L-type calcium channel mediated vessel responses to certain vasoconstrictors among different species. Methods The coronary arteries were dissected from the heart of rats and mice respectively. The coronary arterial ring contraction was measured by Multi Myograph System. Results Endothelin-1, U46619 and 5-HT could produce concentration-dependent vasoconstriction of coronary arterial rings from rats and mice. Compared with rats, the vessel rings of mice were more sensitive to ET-1 and U46619, and less sensitive to 5-HT. The L-type Ca2~ channel blocker nifedipine could significantly inhibit the coronary artery contractions induced by ET-1, U46619 and 5-HT. The inhibitory effect of i ixM nifedipine on ET-1 and 5-HT-induced coronary artery contractions were stronger in mice than in rats, but its effect on U46619 induced-vessel contractions was much weaker in mice than in rats. Conclusions L-type Ca2＋ channel plays an important role in the coronary arterial contraction, but the responses to vasoconstrictor and L-type Ca2＋ channel blocker are different between rats and mice, thus suggesting that the coronary arteries of rats and mice have different biological characteristics.

Highlights for the 6th International Ion Channel Conference:ion channel structure,function,disease and therapeutics

To foster communication and interactions amongst international scholars and scientists in the field of ion channel research, the 6 th International Ion Channel Conference(IICC-2017) was held between June 23–27, 2017 in the eastern coastal city of Qingdao, China. The meeting consisted of 450 attendees and 130 speakers and poster presenters. The program consisted of research progress, new findings and ongoing studies that were focused on(1) Ion channel structure and function;(2) Ion channel physiology and human diseases;(3) Ion channels as targets for drug discovery;(4) Technological advances in ion channel research. An insightful overview was presented on the structure and function of the mechanotransduction channel Drosophila NOMPC(No mechanoreceptor potential C), a member of the transient receptor potential(TRP) channel family. Recent studies on Transmembrane protein 16 or Anoctamin-1(TMEM16A, a member of the calcium-activated chloride channel [CaCC] family) were summarized as well. In addition, topics for ion channel regulation, homeostatic feedback and brain disorders were thoroughly discussed. The presentations at the IICC-2017 offer new insights into our understanding of ion channel structures and functions, and ion channels as targets for drug discovery.

Relaxant Effects of Aike Mixture(艾可合剂) on Isolated Bladder and Prostatic Urethral Smooth Muscle of Rabbits

Objective： To observe the relaxant effect of Aike Mixture （艾可合剂, AKM） on isolated bladder and prostatic urethral smooth muscle of rabbits. Methods： The isolated bladder and prostatic urethral smooth muscle from male rabbits were placed Jn a Magnus bath and smooth muscle contraction was measured using a biological signal acquisition and analysis system. The effects of AKM in combination with methoxyamine, carbachol and CaCl2 on the contractile tension of muscle strips were determined by cumulative dosing. Results： AKM dose-dependently reduced contractile tension of bladder trigone smooth muscle （r=0.831, P〈0.05）, reduced contractile wave amplitude （r=0.837, P〈0.05） and decreased contractile frequency （r=-0.917, P〈0.01）. AKM signJfJcantly inhibited the increases in smooth muscle contraction induced by methoxyamine, carbachol and CaCl2. Conclusion： AKM dose-dependently inhibited the contraction of rabbit isolated bladder and prostatic urethral smooth muscle by antagonizing α1-adrenergic receptors and M-cholinergic receptors.