The occurrence, formation and transformation of disinfection byproducts in the water distribution system: A review.

Disinfection is an effective process to inactivate pathogens in drinking water treatment. However, disinfection byproducts (DBPs) will inevitably form and may cause severe health concerns. Previous research has mainly focused on DBPs formation during the disinfection in water treatment plants. But few studies paid attention to the formation and transformation of DBPs in the water distribution system (WDS). The complex environment in WDS will affect the reaction between residual chlorine and organic matter to form new DBPs. This paper provides an overall review of DBPs formation and transformation in the WDS. Firstly, the occurrence of DBPs in the WDS around the world was cataloged. Secondly, the primary factors affecting the formation of DBPs in WDS have also been summarized, including secondary chlorination, pipe materials, biofilm, deposits and coexisting anions. Secondary chlorination and biofilm increased the concentration of regular DBPs (e.g., trihalomethanes (THMs) and haloacetic acids (HAAs)) in the WDS, while Br- and I- increased the formation of brominated DBPs (Br-DBPs) and iodinated DBPs (I-DBPs), respectively. The mechanism of DBPs formation and transformation in the WDS was systematically described. Aromatic DBPs could be directly or indirectly converted to aliphatic DBPs, including ring opening, side chain breaking, chlorination, etc. Finally, the toxicity of drinking water in the WDS caused by DBPs transformation was examined. This review is conducive to improving the knowledge gap about DBPs formation and transformation in WDS to better solve water supply security problems in the future.

Study on the operation performance and floc adhesion mechanism of dissolved air flotation equipment.

As a critical air dissolving system, the performance of air flotation equipment directly determines the adhesion efficiency and pollutant removal efficiency of air flotation processes. The factors affecting the performance of air flotation equipment and the relationships between equipment performance and pollution removal efficiency were studied. The results show that when the dissolved gas pressure was 0.4 MPa and the air intake rate was 24 mL/min, the dissolved gas efficiency of the equipment reached its highest value of 55%, the average particle size of bubbles was maintained at 24 µm, and the dissolved oxygen (DO) content significantly increased. When the dissolved gas pressure was 0.4 MPa, the air intake rate was 24 mL/min, and the coagulant dose was 6 mg/L; the removal rates for turbidity, chlorophyll-a, total organic carbon (TOC), and UV absorbance at 254 nm (UV254) reached 95.76%, 96.41%, 34.21%, and 65.96%, respectively. The degree of pollutant removal was positively correlated with changes to the equipment performance parameters. Microbubbles (MBs) showed good removal of high-molecular weight, strongly hydrophobic organic matter and showed some removal of the trihalomethane formation potential (THMFP) of the water. The removal mechanism mainly depended on the hydrophobic interactions of the MBs with algae and organic matter. The flocs and MBs collided and adhered to form air-entrained flocs. The separation of air-entrained flocs depended on the relationship between the surface load and the rising velocity. The surface load has to be lower than the rising velocity of the minimum air-entrained flocs to ensure good effluent outcomes.

Pilot-scale and mechanistic study of the degradation of typical odors and organic compounds in drinking water by a combined UV/H2O2-BAC process.

Odor problems are challenging issues in water treatment. Advanced oxidation has a significant degradation effect on these odors; however, some issues, such as oxidant residues and disinfection byproducts, exist in the use of advanced oxidation in actual water treatment. Because of the above issues, a combined advanced oxidation process has emerged-the UV/H2O2 -biological activated carbon (BAC) process can play a strong oxidizing role in advanced oxidation and uses the physical adsorption and biological effects of activated carbon. However, there have been few studies on the odor degradation mechanism and characteristics of activated carbon biofilms in actual water treatment. This paper systematically studied the organic and odor substances removal effects and mechanism of a pilot combined UV/H2O2-BAC process. The results showed that UV/H2O2-BAC technology had a good removal effect on odor substances under long-term stable operation. The concentrations of geosmin (GSM) and 2-methylisoborneol (2-MIB) after systemic treatment were below 5 ng/L. The removal rates of DOC, UV254 and H2O2 by the combined process were 53.60%, 73.08% and 60.20%, respectively. The results of full-scan determination of GSM and 2-MIB degradation by gas chromatography-mass spectrometry (GC-MS) were consistent with those of front-track analysis. The diversity, richness and evenness of microorganisms in the lower activated carbon layer were higher than those in the middle and upper activated carbon layers. The greater the difference in the carbon layer height was, the greater the difference in the biological community structure.

Comparison of fleroxacin oxidation by chlorine and chlorine dioxide: Kinetics, mechanism and halogenated DBPs formation.

Fleroxacin (FLE) is a widely used fluoroquinolones to cure urinary tract infections and respiratory disease, which has been frequently detected in the aquatic environment. The reactivity kinetics of FLE by chlorine and chlorine dioxide (ClO2) and transformation mechanism were investigated in this study. The results showed that FLE was degraded efficiently by chlorine and ClO2, and both reactions followed second-order kinetics overall. The increase of disinfectant dosage and temperature would enhance the degradation of FLE. The highest removal of FLE by chlorine was achieved at a neutral condition (pH 7.4), whereas ClO2 reaction rates increased dramatically with the increasing pH in this study condition. The number of intermediates identified in FLE chlorination and ClO2 oxidation was seven and ten, respectively. The piperazine ring cleavage was the principal and initial reaction in both above reactions. Then, the removal of the piperazine group was predominantly in FLE removal by chlorine, while the decarboxylation mainly occurred in FLE removal by ClO2. The intermediates increased first and then decreased with time, while three kinds of halogenated DBPs increased with time, indicating the above-identified intermediates were further transformed to the halogenated DBPs. Additionally, compared to chlorine reaction, the reaction of ClO2 with FLE reduced the formation of halogenated DBPs, but it also induced the formation of chlorite. The analysis of toxicity showed that compared with chlorination, the oxidation of ClO2 was more suitable for FLE removal.

Investigation on combined copy number variation sequencing and cytogenetic karyotyping for prenatal diagnosis.

BACKGROUND: We aimed to evaluate the clinical value of copy number variation-sequencing (CNV-Seq) in combination with cytogenetic karyotyping in prenatal diagnosis. METHODS: CNV-Seq and cytogenetic karyotyping were performed in parallel for 9452 prenatal samples for comparison of the diagnostic performance of the two methods, and to evaluate the screening performance of maternal age, maternal serum screening, fetal ultrasound scanning and noninvasive prenatal testing (NIPT) for fetal pathogenic copy number variation (CNV). RESULTS: Among the 9452 prenatal samples, traditional karyotyping detected 704 cases (7.5%) of abnormal cytogenetic karyotypes, 171 (1.8%) chromosome polymorphism, 20 (0.2%) subtle structural variations, 74 (0.7%) mutual translocation (possibly balanced), 52 (0.6%) without karyotyping results, and 8431 (89.2%) normal cytogenetic karyotypes. Among the 8705 cases with normal karyotype, polymorphism, mutual translocation, or marker chromosome, CNV-Seq detected 63 cases (0.7%) of pathogenic chromosome microdeletion/duplication. Retrospectively, noninvasive prenatal testing (NIPT) had high sensitivity and specificity for the screening of fetal pathogenic CNV, and NIPT combining with maternal age, maternal serum screening or fetal ultrasound scanning, which improved the screening performance. CONCLUSION: The combined application of cytogenetic karyotyping and CNV-Seq significantly improved the detection rate of fetal pathogenic chromosome microdeletion/duplication. NIPT was recommended for the screening of pathogenic chromosome microdeletion/duplication, and NIPT combining with other screening methods further improved the screening performance for pathogenic fetal CNV.

Characterization of enoxacin (ENO) during ClO2 disinfection in water distribution system: Kinetics, byproducts, toxicity evaluation and halogenated disinfection byproducts (DBPs) formation potential.

Enoxacin (ENO) is widespread in water because it is commonly used as a human and veterinary antibiotic. However, little effort has been dedicated to revealing the transformation mechanisms of ENO destruction using ClO2, especially within a water distribution system (WDS). To address this knowledge gap, the kinetics, byproducts, toxicity, and formation potential of halogenated disinfection byproducts (DBPs) associated with ENO destruction using ClO2 in a pilot-scale PE pipe was explored for the first time. Statistical analyses showed that the destruction efficiency of ENO in the pilot-scale PE pipe was lower than that in deionized water (DI water), and the reactions in DI water followed the second-order kinetic model. Furthermore, pH has a significant effect on the destruction of ENO, and the removal ratio increased at a higher pH. Additionally, increasing the flow rate elevated the ENO removal efficiency; however, the influence of flow velocity was limited to ENO destruction. The ENO removal rates within the diverse pipes exhibited the following order: stainless steel pipe < PE pipe < ductile iron pipe. Nine possible intermediates were identified, and those that were formed by piperazine group cleavage represented the major primary byproducts of the entire destruction process. Additionally, the ENO destruction in a pilot-scale PE pipe had minimal influence on halogenated DBPs and chlorite formation. Finally, the toxicity evaluation illustrated that the presence of ENO increased the potential risk of water quality safety when treated with ClO2.

Study on correlation between coagulation indexes and disease progression in patients with cirrhosis.

OBJECTIVE: To inquire into the significance of coagulation indexes in the progression of cirrhosis. METHODS: A total of 108 patients with cirrhosis treated in our hospital were collected as the research group (RG), and 105 healthy people who underwent concurrent physical examination were selected as the control group (CG). The coagulation indexes of all the participants were tested to determine their significance in cirrhosis progression. RESULTS: Compared with the CG, prothrombin time (PT), activated partial thrombin time (APTT) and thrombin time (TT) in the RG were statistically prolonged, while fibrinogen (FIB) was notably decreased (P<0.05). With the increase of Child-Pugh score, PT, APTT and TT prolonged and FIB reduced gradually (P<0.05). The coagulation indexes of patients were correlated with Child-Pugh score (P<0.05). Patients in the RG showed markedly higher alanine aminotransferase (ALT), total bilirubin (TBil), total bile acid (TBA), mean platelet volume (MPV), platelet distribution width (PDW) and platelet-large cell ratio (P-LCR), with notably lower albumin (ALB), prealbumin (PA), platelet count (PLT) and coagulation factors compared with the CG. As the Child-Pugh score increased, the ALT, TBil, TBA, MPV, PDW and P-LCR gradually elevated in the RG (P<0.05), whilst coagulation factors, ALB, PLT and PA all gradually decreased (P<0.05). The value of area under the curve (AUC) of each coagulation index for early diagnosis of cirrhosis was >0.80, and the sensitivity was >80% (P<0.05). CONCLUSION: Coagulation indexes, coagulation factors, platelet parameters and liver function all effectively reflect the level of liver injury; especially which, coagulation indexes are related to the severity of liver injury, and can provide evidence for the early diagnosis of cirrhosis patients, with clinical significance.

Impacts of pre-oxidation on the formation of disinfection byproducts from algal organic matter in subsequent chlor(am)ination: A review.

Algae cells and algal organic matter (AOM) present in algae impacted source water pose a serious threat to the safety of drinking water. Conventional water treatment processes poorly remove AOM that can transform to harmful disinfection byproducts (DBPs) during ensuing disinfection. This article offers a comprehensive review on the impacts of pre-oxidation on the formation of DBPs from AOM in subsequent chlor(am)ination. Various characterization techniques for algal cells and AOM are first overviewed with an effort to better understanding of correlation between the AOM properties and downstream DBP formation. Then, the present work reviews recent studies on application of different pre-oxidation technologies, such as chlor(am) ination, UV irradiation, ozonation, ferrate (VI), permanganate oxidation and UV-based advanced oxidation processes (AOPs), to remove algal cells and degrade AOM. Pre-oxidation can reduce the stability of algal cells and inactivate algal cells for promoting cell aggregation and thus favoring coagulation. Meanwhile, pre-oxidation can mitigate and degrade AOM into small molecular weight organic compounds to reduce DBP formation potential during subsequent chlor(am)ination. Finally, this review provides an overall evaluation on the applicability of different pre-oxidation processes, and identifies future research demands.

Calmodulin mutant in central linker reduces the binding affinity with PreIQ and IQ while interacting with CaV1.2 channels.

Calmodulin (CaM) was reported to interact with PreIQ and IQ of CaV1.2 channels, but to date, no explicit binding sites of CaM were illustrated. Therefore, in the present study, we firstly used MOE (Molecular Operating Environment) for protein-protein docking and we found that the most likely residues of CaM that play an important role in the interface are concentrated in central linker region. Next we examined the binding properties of CaM and its mutants to PreIQ and IQ by GST pull-down assays. Here we confirmed that CaM binds to PreIQ and IQ in a concentration-dependent and [Ca2+]-dependent manner. However, silencing the effect of N-lobe and C-lobe by mutating two Ca2+ binding sites of each lobe abolished [Ca2+]-dependence of CaM binding, but could not influence the combination. And the mutant in central linker reduced the binding of CaM/PreIQ and CaM/IQ especially at low [Ca2+]. We confirmed that N-lobe and C-lobe play vital role in sensing the change of Ca2+, and found that the central linker of CaM is involved in the binding of CaM to CaV1.2 channels in particular at low [Ca2+], not only participates in the combination with PreIQ, but also with IQ.

Assessing the global resilience of water quality sensor placement strategies within water distribution systems.

Water quality sensors are often spatially distributed in water distribution systems (WDSs) to detect contamination events and monitor quality parameters (e.g., chlorine residual levels), thereby ensuring safety of a WDS. The performance of a water quality sensor placement strategy (WQSPS) is not only affected by sensor spatial deployment that has been extensively analyzed in literature, but also by possible sensor failures that have been rarely explored so far. However, enumerating all possible sensor failure scenarios is computationally infeasible for a WQSPS with a large number of sensors. To this end, this paper proposes an evolutionary algorithm (EA) based method to systematically and efficiently investigate the WQSPS' global resilience considering all likely sensor failures. First, new metrics are developed in the proposed method to assess the global resilience of a WQSPS. This is followed by a proposal of an efficient optimization approach based on an EA to identify the values of global resilience metrics. Finally, the sensors within the WQSPS are ranked to identify their relative importance in maintaining the WQSPS's detection performance. Two real-world WDSs with four WQSPSs for each case study are used to demonstrate the utility of the proposed method. Results show that: (i) compared to the traditional global resilience analysis method, the proposed EA-based approach identifies improved values of global resilience metrics, (ii) the WQSPSs that deploy sensors close to large demand users are overall more resilient in handling sensor failures relative to other design solutions, thus offering important insight to facilitate the selection of WQSPSs, and (iii) sensor rankings based on the global resilience can identify those sensors whose failure would significantly reduce the WQSPS's performance thereby providing guidance to enable effective water quality sensor management and maintenance.

First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases.

BACKGROUND: It is well known that second-trimester maternal serum alpha-fetoprotein (MS-AFP) is a predictor for adverse pregnancy outcomes (APOs), such as preterm birth, stillbirth, preeclampsia and small for gestational age (SGA). However, it is unknown whether first-trimester MS-AFP is also predictive of APOs. METHODS: We retrospectively reviewed the data on the first-trimester MS-AFP levels and pregnancy outcomes of 3325 singleton pregnant women. The cutoff value of 2.5 multiple of the median (MoM) was used to evaluate the risks of APOs regarding MS-AFP. The receiver operating characteristic (ROC) curves were used to evaluate the predictive efficiencies of MS-AFP to these disorders. RESULTS: A total of 181 pregnancies resulted in preterm birth, 32 in stillbirth, 81 in preeclampsia, and 362 in SGA. Compared to women with MS-AFP < 2.5MoM, those with MS-AFP ≥ 2.5MoM had increased risks (odds ratio, 95% confidence interval) of preterm birth (2.53, 1.65~3.88), preeclampsia (3.05, 1.71~5.43) and SGA (1.90, 1.34~2.69), and had an earlier distribution of gestational weeks at delivery (P = 0.004) and a lower distribution of neonatal birth weights (P = 0.000), but the actual between-group differences were minuscule. The areas under ROC curves were 0.572 (P = 0.001), 0.579 (P = 0.015) and 0.565 (P = 0.000) for preterm birth, preeclampsia and SGA, respectively. Subdivisions for the disorders did not obviously improve the performances of MS-AFP. CONCLUSIONS: Elevated first-trimester MS-AFP is associated with increased risk of preterm birth, preeclampsia and SGA. However, the predictive efficiencies were low and it is not a good predictor for these APOs.

Chlorination of enoxacin (ENO) in the drinking water distribution system: Degradation, byproducts, and toxicity.

Chlorine is widely used as a drinking water disinfectant to ensure water security. However, the transformation mechanisms of its degradation of emerging pollutants within the water distribution system (WDS) is insufficiently understood. Thus, the kinetics, degradation byproducts, and toxicity of the chlorination of enoxacin (ENO, a type of emerging pollutant) were explored in a pilot-scale WDS for the first time. It was found that the chlorination rate of ENO was higher in deionized water (DW) than in the pilot-scale WDS, and the degradation followed second-order kinetics in DW. The degradation efficiency was found to be sensitive to pH, and was highest at a pH of 7.4. The chlorination rate of ENO increased with increasing temperature in both DW and WDS. For different pipe materials, the relative performance of ENO chlorination efficiency followed the order of steel pipe > ductile iron pipe > polyethylene (PE) pipe. Seven intermediates were identified during ENO chlorination, and the primary oxidation reaction involved the cleavage of the piperazine group. Finally, it was found that the potential for chlorine toxicity in treated drinking water in the presence of ENO is higher than it is without this pollutant.

Sulfadiazine destruction by chlorination in a pilot-scale water distribution system: Kinetics, pathway, and bacterial community structure.

Sulfadiazine (SDZ) has been frequently detected in surface waters in recent years. We evaluated the kinetics, mechanisms, intermediate products and bacterial community structure that result from the reaction of SDZ with free chlorine (HOCl/OCl-). We examined this in a pilot-scale water distribution system. Neutral pH had the fastest rate of destruction of SDZ. A second-order reaction constant for the destruction of SDZ by chlorine increased with increasing concentration of free chlorine (FC). For different pipe materials, the rate of SDZ degradation decreased as follows: stainless steel (SS) pipe > polyethylene (PE) pipe > ductile iron (DI) pipe. Based on the less complex bacterial diversity and more chlorine-resistant by 16S ribosomal ribonucleic acid (rRNA) gene analysis, SS pipe and PE pipe were more suitable in SDZ degradation in water distribution system (WDS) than DI pipe. In addition, the transformation products from SDZ chlorination were identified by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry, and the products included SO2 extrusion products, haloacetic acids and trihalomethanes. Toxicity tests further confirmed that the toxicity of SDZ chlorination was higher both in low FC (0.7 mg/L) and high FC (1.3 mg/L) in WDS.

An efficient multi-objective optimization method for water quality sensor placement within water distribution systems considering contamination probability variations.

Water quality security within water distribution systems (WDSs) has been an important issue due to their inherent vulnerability associated with contamination intrusion. This motivates intensive studies to identify optimal water quality sensor placement (WQSP) strategies, aimed to timely/effectively detect (un)intentional intrusion events. However, these available WQSP optimization methods have consistently presumed that each WDS node has an equal contamination probability. While being simple in implementation, this assumption may do not conform to the fact that the nodal contamination probability may be significantly regionally varied owing to variations in population density and user properties. Furthermore, the low computational efficiency is another important factor that has seriously hampered the practical applications of the currently available WQSP optimization approaches. To address these two issues, this paper proposes an efficient multi-objective WQSP optimization method to explicitly account for contamination probability variations. Four different contamination probability functions (CPFs) are proposed to represent the potential variations of nodal contamination probabilities within the WDS. Two real-world WDSs are used to demonstrate the utility of the proposed method. Results show that WQSP strategies can be significantly affected by the choice of the CPF. For example, when the proposed method is applied to the large case study with the CPF accounting for user properties, the event detection probabilities of the resultant solutions are approximately 65%, while these values are around 25% for the traditional approach, and such design solutions are achieved approximately 10,000 times faster than the traditional method. This paper provides an alternative method to identify optimal WQSP solutions for the WDS, and also builds knowledge regarding the impacts of different CPFs on sensor deployments.

Chlorine decay and trihalomethane formation following ferrate(VI) preoxidation and chlorination of drinking water.

This paper presents the effect of preoxidation with ferrate(VI) (FeVIO42-, Fe(VI)) prior to chlorination on chlorine decay and formation of disinfection by-products in filtered raw water from a full-scale drinking water treatment plant. The rate of chlorine decay became significantly faster as the concentration of ferrate(VI) increased. Chlorine degradation followed two first-order decay reactions with rate constants k1 and k2 for fast and slow decay, respectively. Kinetic modeling established the relationships between k1 and k2 and varying dosages of chlorine and ferrate(VI). When ferrate(VI) was used as a pre-oxidant, the levels of trihalomethanes (trichloromethane (TCM), dichlorobromomethane (DCBM), dibromochloromethane (DBCM), and tribromomethane (TBM)) in water samples decreased as the ferrate(VI) concentration increased. The concentrations of these trihalomethanes followed the order TCM > DCBM ≈ DBCM > TBM.

Chloramines in a pilot-scale water distribution system: Transformation of 17ß-estradiol and formation of disinfection byproducts.

The degradation and transformation products of 17ß-estradiol (E2) by chloramines in a pilot-scale water distribution system (WDS) were investigated using varying conditions including multiple mass ratios of chlorine to nitrogen (Cl/N), changing concentrations of chloramines, and different pH and pipe materials. The degradation of E2 was complete in ≤9 h in both deionized water (DW) and in the WDS under studied conditions. When the degradation rate of E2 was compared in WDS and DW, the degradation rate was appreciably greater in the WDS than in the DW at Cl/N mass ratios of 3, 4 and 6. However, at Cl/N mass ratios of 8 and 9, degradation was faster in the DW than in the WDS. The degradation rate of E2 was greatly affected by the initial total chloramine concentration, and the degradation of E2 in DW was consistent with second-order kinetics. The degradation rate of E2 in both the DW and the WDS increased with increasing pH. The order of degradation rate of E2in different pipes was: ductile iron loop (loop A) > polyethylene (PE) loop (loop B)> stainless steel loop (loop C). Ten specific degradation products of E2, produced by chloramination, were identified. Most of the degradation products of E2 chloramination were stable for more than 10 h. The degradation pathways of E2 in the WDS are proposed and briefly discussed. The concentrations of trihalomethanes (THMs), haloacetic acids (HAAs), and halogenated nitromethane (HNMs) during the degradation E2 in WDS were also determined.

The individual N- and C-lobes of calmodulin tether to the Cav1.2 channel and rescue the channel activity from run-down in ventricular myocytes of guinea-pig heart.

The present study examined the binding of the individual N- and C-lobes of calmodulin (CaM) to Cav1.2 at different Ca(2+) concentration ([Ca(2+)]) from ≈ free to 2mM, and found that they may bind to Cav1.2 Ca(2+)-dependently. In particular, using the patch-clamp technique, we confirmed that the N- or C-lobes can rescue the basal activity of Cav1.2 from run-down, demonstrating the functional relevance of the individual lobes. The data imply that at resting [Ca(2+)], CaM may tether to the channel with its single lobe, leading to multiple CaM molecule binding to increase the grade of Ca(2+)-dependent regulation of Cav1.2.

Lobe-related concentration- and Ca(2+)-dependent interactions of calmodulin with C- and N-terminal tails of the CaV1.2 channel.

This study examined the bindings of calmodulin (CaM) and its mutants with the C- and N-terminal tails of the voltage-gated Ca(2+) channel CaV1.2 at different CaM and Ca(2+) concentrations ([Ca(2+)]) by using the pull-down assay method to obtain basic information on the binding mode, including its concentration- and Ca(2+)-dependencies. Our data show that more than one CaM molecule could bind to the CaV1.2 C-terminal tail at high [Ca(2+)]. Additionally, the C-lobe of CaM is highly critical in sensing the change of [Ca(2+)] in its binding to the C-terminal tail of CaV1.2, and the binding between CaM and the N-terminal tail of CaV1.2 requires high [Ca(2+)]. Our data provide new details on the interactions between CaM and the CaV1.2 channel.

Effects of astragaloside IV on action potentials and ionic currents in guinea-pig ventricular myocytes.

Astragaloside IV (AS-IV) is one of the main active constituents of Astragalus membranaceus, which has various actions on the cardiovascular system. However, its electrophysiological mechanisms are not clear. In the present study, we investigated the effects of AS-IV on action potentials and membrane currents using the whole-cell patch clamp technique in isolated guinea-pig ventricular myocytes. AS-IV prolonged the action potential duration (APD) at all three tested concentrations. The peak effect was achieved with 1×10(-6) M, at which concentration AS-IV significantly prolonged the APD at 95% repolarization from 313.1±38.9 to 785.3±83.7 ms. AS-IV at 1×10(-6) M also enhanced the inward rectifier K(+) currents (I(K1)) and inhibited the delayed rectifier K(+) currents (I(K)). AS-IV (1×10(-6) M) strongly depressed the peak of voltage-dependent Ca(2+) channel current (I(CaL)) from -607.3±37.5 to -321.1±38.3 pA. However, AS-IV was not found to affect the Na(+) currents. Taken together, AS-IV prolonged APD of guinea-pig ventricular myocytes, which might be explained by its inhibition of I(K). AS-IV also influences Ca(2+) signaling through suppressing ICaL.

The up-regulation of voltage-gated sodium channels subtypes coincides with an increased sodium current in hippocampal neuronal culture model.

Voltage-gated sodium channels (VGSC) have been linked to inherited forms of epilepsy. The expression and biophysical properties of VGSC in the hippocampal neuronal culture model have not been clarified. In order to evaluate mechanisms of epileptogenesis that are related to VGSC, we examined the expression and function of VGSC in the hippocampal neuronal culture model in vitro and spontaneously epileptic rats (SER) in vivo. Our data showed that the peak amplitude of transient, rapidly-inactivating Na(+) current (I(Na,T)) in model neurons was significantly increased compared with control neurons, and the activation curve was shifted to the negative potentials in model neurons in whole cell recording by patch-clamp. In addition, channel activity of persistent, non-inactivating Na(+) current (I(Na,P)) was obviously increased in the hippocampal neuronal culture model as judged by single-channel patch-clamp recording. Furthermore, VGSC subtypes Na(V)1.1, Na(V)1.2 and Na(V)1.3 were up-regulated at the protein expression level in model neurons and SER as assessed by Western blotting. Four subtypes of VGSC proteins in SER were clearly present throughout the hippocampus, including CA1, CA3 and dentate gyrus regions, and neurons expressing VGSC immunoreactivity were also detected in hippocampal neuronal culture model by immunofluorescence. These findings suggested that the up-regulation of voltage-gated sodium channels subtypes in neurons coincided with an increased sodium current in the hippocampal neuronal culture model, providing a possible explanation for the observed seizure discharge and enhanced excitability in epilepsy.