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.

Theoretical analyses on bed topography responses in large depth-to-width ratio river bends with constant curvatures

Bed morphology is the result of a dynamic response to a complex meandering river system. It is an important factor for the further development of river. Based on the meandering river characterized by a large depth-to-width ratio, a theoretical model is established with the coupling of Navier-Stokes （N-S）~ sediment transport, and bed deformation equations. The flow characteristics and bed response of river are obtained with the perturbation method. The research results show that, under the effect of two- dimensional flow disturbance, the bars and pools present the regular response. For a given sinuousness, the amplitude of the bed response can be used as a criterion to judge the bedform stability. The effects of the Reynolds number, disturbance wavenumber, sinuousness, and bed morphology gradient on the bed response development are described.

A NEW LARGE CAVITATION CHANNEL IN CHINA SHIP SCIENTIFIC RESEARCH CENTER

After about 10 years' runing of the LCC (DTRC, USA) and the HYKAT( HSVA,Germany) , another new large cavitation channel with low background noise is to be in operation inChina Ship Scientific Research Center(CSS-RC), Wuxi, China. The important specific properties of thechannel are the large test section (2. 0 m in height, 2. 2 m in width and 10. 5 m in length) , themaximum speed of more than 15 m/s, the low turbulence level, the low background noise of the wholefacility, together with the new noise measurement system. So large scale models can be tested withonly minor wall effects and at high Renolds numbers, and the pretentious acoustical measurements canbe performed. This paper describes the features of the new channel and the first test resultsobtained during extensive calibration and validation.

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.

otassium channels in airway smooth muscle and airway hyperreactivity in asthma

Our knowledge of the physiology of ion channels has increased tremendously during the past 20 years because of the advances of the single-channel recording and molecular cloning techniques. More than 50 different identified potassium channels have already been found.1,2 They are distributed ubiquitously in wide variety of cells including airway smooth muscle （ASM） cells and inflammatory cells in airway such as eosinophils, basophils, macrophages and so on.3 Several types of K+ channels have been identified in ASM cells, e.g., a large-conductance, voltgage-dependent Ca2+-activated K+ channel(BKCa), a voltage-dependent delayed-rectifier K+ channel（Kv）, and an ATP-sensitve K+ channel(KATP).1 In such excitable cells,

Forensic Significance of Messenger RNA and Protein Expression of Genes Downstream of Hypoxia Inducible Factor 2 in Myocardial Tissue for Death Discrimination

Background: As a heterodimeric transcription factor, hypoxia-inducible factor 2 alpha subunit (HIF2A), is an important member of the HIF family. It plays a significant role in the hypoxia adaptation process by regulating the different types of downstream transcription factors and auxiliary regulatory factors. HIF2A-related factors are believed to participate in the progression of myocardial injury or myocardial ischemia, support the protection of ischemic myocardium, and provide guiding significance for the diagnosis and discrimination of sudden cardiac death in forensic pathology. Aim and Objectives: This study aimed to explore the discriminability and applicability of HIF2A-related factors in myocardial infarction cases compared with other causes of death, provide further insights for the forensic diagnosis of heart failure (HF) cases with myocardial infarction, and support the clinical treatment of patients with HF after myocardial infarction. Materials and Methods: The relative expression levels of HIF2A, amphiregulin (AREG), potassium large conductance calcium-activated channel subfamily M β1 (KCNMB1), peroxisome proliferator-activated receptor α (PPARA), vascular endothelial growth factor (VEGF), and VEGFR2 messenger RNAs (mRNAs) in myocardial tissue samples were performed using quantitative reverse transcriptase-polymerase chain reaction. A partial least squares-discriminant analysis model was constructed to select the indicators with better identification effects for myocardial infarction cases. The protein levels of HIF2A, AREG, KCNMB1, and PPARA were further detected by immunohistochemistry. The forensic autopsy cases (27 cases in total, postmortem interval <72 h) included seven cases of acute myocardial infarction and ten cases of myocardial ischemia. There were ten cases in the control group, including four cases of traffic injury, one case of injury by fall from height, and five cases of blunt force injury. Results: Characteristic results were observed in the myocardial ischemia/infarction samples. Compared with the control group, the relative mRNA expression levels of AREG, KCNMB1, and PPARA were significantly increased during the progression of myocardial ischemia, but this was not observed for HIF2A, VEGF, or VEGFR2 mRNA. Immunohistochemistry assays further verified the expression levels of the related factors at the protein level, and H and E staining showed signs of angiogenesis and inflammation in the ischemia/infarction group. Conclusions: By controlling the expression of downstream target genes (AREG, KCNMB1, and PPARA) during myocardial cell hypoxia adaptation, HIF2A has a potential significance in the diagnosis of myocardial infarction in forensic medicine. We believe that HIF2A, AREG, KCNMB1, and PPARA can be used as molecular pathological biomarkers for the discrimination of causes of death in myocardial infarction cases.

A new muon-pion collection and transport system design using superconducting solenoids based on CSNS

A new muon and pion capture system is proposed for the China Spallation Neutron Source （CSNS）, currently under construction. Using about 4% of the pulsed proton beam （1.6 GeV, 4 kW and 1 Hz） of CSNS to bombard a cylindrical graphite target inside a superconducting solenoid, both surface muons and pions can be acquired. The acceptance of this novel capture system - a graphite target wrapped up by a superconducting solenoid - is larger than the normal muon beam lines using quadrupoles at one side of the separated muon target. The muon and pion production at different capture magnetic fields was calculated using Geant4. The bending angle of the capture solenoid with respect to the proton beam was also optimized in simulation to achieve more muons and pions. Based on the layout of the muon experimental area reserved at the CSNS project, a preliminary muon beam line was designed with multi-purpose muon spin rotation areas （surface, decay and low-energy muons）. Finally, high-flux surface muons （10S/s） and decay muons （109/s） simulated by G4beamline will be available at the end of the decay solenoid based on the first phase of CSNS. This collection and transport system will be a very effective beam line at a proton current of 2.5uA.