Conformational changes underlying pore dilation in the cytoplasmic domain of mammalian inward rectifier K^+ channels

Inanobe A, Nakagawa A, Kurachi Y (2013) Conformational Changes Underlying Pore Dilation in the Cytoplasmic Domain of Mammalian Inward Rectifier K^+ Channels. PLOS ONE 8(11): e79844. https://doi.org/10.1371/journal.pone.007984

Interactions of Cations with the Cytoplasmic Pores of Inward Rectifier K^+ Channels in the Closed State

This research was originally published in Journal of Biological Chemistry. Atsushi Inanobe, Atsushi Nakagawa, and Yoshihisa Kurachi. Interactions of Cations with the Cytoplasmic Pores of Inward Rectifier K^+ Channels in the Closed State. Journal of Biological Chemistry. 2011; 286, 41801-41811. © the American Society for Biochemistry and Molecular Biology

A structural determinant for the control of PIP_2 sensitivity in G protein-gated inward rectifier K^+ channels

Inward rectifier K^+ (Kir) channels are activated by phosphatidylinositol-( 4,5)-bisphosphate (PIP_2), but G protein-gated Kir (K_G) channels further require either G protein βγ subunits (Gβγ) or intracellular Na^+ for their activation. To reveal the mechanism(s) underlying this regulation, we compared the crystal structures of the cytoplasmic domain of K_G channel subunit Kir3.2 obtained in the presence and the absence of Na^+. The Na^+ -free Kir3.2, but not the Na^+ -plus Kir3.2, possessed an ionic bond connecting the N terminus and the CD loop of the C terminus. Functional analyses revealed that the ionic bond between His-69 on theNterminus and Asp-228 on the CD loop, which are known to be critically involved in Gβγ- and Na^+ -dependent activation, lowered PIP_2 sensitivity. The conservation of these residues within the K_G channel family indicates that the ionic bond is a character that maintains the channels in a closed state by controlling the PIP_2 sensitivity.This research was originally published in Journal of Biological Chemistry. Atsushi Inanobe, Atsushi Nakagawa, Takanori Matsuura and Yoshihisa Kurachi. A structural determinant for the control of PIP2 sensitivity in G protein-gated inward rectifier K^+ channels. Journal of Biological Chemistry. 2010; 285, 38517-38523. © the American Society for Biochemistry and Molecular Biology

Eucalyptus Leaf Extract Suppresses the Postprandial Elevation of Portal, Cardiac and Peripheral Fructose Concentrations after Sucrose Ingestion in Rats

Overintake of sucrose or fructose induces adiposity. Fructose undergoes a strong Maillard reaction, which worsens diabetic complications. To determine whether Eucalyptus globulus leaf extract (ELE) suppresses the postprandial elevation of serum fructose concentrations (SFCs) in the portal, cardiac, and peripheral blood after sucrose ingestion, we performed gas chromatography/mass spectrometry (GC/MS) and measured SFC without any interference by contaminating glucose in the samples. Fasting Wistar rats were orally administered water (control group) or ELE (ELE group) before sucrose ingestion. Blood was collected from the portal vein, heart, and tail. The increase in the SFCs in the portal and cardiac samples 30 min after sucrose ingestion was lower in the ELE group than in the control group. The coefficient of correlation between the SFCs in the portal and cardiac samples was 0.825. The peripheral SFC in the control group progressively increased and was 146 µmol/L at 60 min. This increase was significantly lower in the ELE group. In contrast, the serum glucose concentrations in the 2 groups were similar. ELE suppressed postprandial hyperfructosemia in the portal, cardiac, and peripheral circulations. ELE may counteract glycation caused by high blood fructose concentrations induced by the consumption of fructose-containing foods or drinks

General Survey of Tohoku Hybrid Magnet System(Part I. Establishment and Tests of Hybrid Magnet System at HFLSM)

Outline of Tohoku Hybrid Magnet system is briefly described. High Field Laboratory was established in the Research Institute for Iron, Steel and Other Metals, Tohoku University, in 1981, for accelerating research and development of high field superconducting materials. Three hybrid magnets generating magnetic fields more than 20 T have been constructed as its main apparatuses. The strongest hybrid magnet, HM-1, could produce 31.1 T in November, 1986, which was the world record as this kind of hybrid magnet. Several important features of the hybrid magnet system are introduced which will be also useful to understand the following papers

Ischemic and Bleeding Risk After Percutaneous Coronary Intervention in Patients With Prior Ischemic and Hemorrhagic Stroke

Background: Prior stroke is regarded as risk factor for bleeding after percutaneous coronary intervention (PCI). However, there is a paucity of data on detailed bleeding risk of patients with prior hemorrhagic and ischemic strokes after PCI. Methods and Results: In a pooled cohort of 19 475 patients from 3 Japanese PCI studies, we assessed the influence of prior hemorrhagic (n=285) or ischemic stroke (n=1773) relative to no-prior stroke (n=17 417) on ischemic and bleeding outcomes after PCI. Cumulative 3-year incidences of the co-primary bleeding end points of intracranial hemorrhage, non-intracranial global utilization of streptokinase and tissue plasminogen activator for occluded coronary arteries (GUSTO) moderate/severe bleeding, and the primary ischemic end point of ischemic stroke/myocardial infarction were higher in the prior hemorrhagic and ischemic stroke groups than in the no-prior stroke group (6.8%, 2.5%, and 1.3%, P<0.0001, 8.8%, 8.0%, and 6.0%, P=0.001, and 12.7%, 13.4%, and 7.5%, P<0.0001). After adjusting confounders, the excess risks of both prior hemorrhagic and ischemic strokes relative to no-prior stroke remained significant for intracranial hemorrhage (hazard ratio (HR) 4.44, 95% CI 2.64-7.01, P<0.0001, and HR 1.52, 95% CI 1.06-2.12, P=0.02), but not for non-intracranial bleeding (HR 1.18, 95% CI 0.76-1.73, P=0.44, and HR 0.94, 95% CI 0.78-1.13, P=0.53). The excess risks of both prior hemorrhagic and ischemic strokes relative to no-prior stroke remained significant for ischemic events mainly driven by the higher risk for ischemic stroke (HR 1.46, 95% CI 1.02-2.01, P=0.04, and HR 1.49, 95% CI 1.29-1.72, P<0.0001). Conclusions: Patients with prior hemorrhagic or ischemic stroke as compared with those with no-prior stroke had higher risk for intracranial hemorrhage and ischemic events, but not for non-intracranial bleeding after PCI

Prognostic Impact of Baseline Hemoglobin Levels on Long-Term Thrombotic and Bleeding Events After Percutaneous Coronary Interventions

Background: Association of baseline hemoglobin levels with long-term adverse events after percutaneous coronary interventions has not been yet thoroughly defined. We aimed to assess the clinical impact of baseline hemoglobin on long-term ischemic and bleeding risk after percutaneous coronary intervention. Methods and Results: Using the pooled individual patient-level data from the 3 percutaneous coronary intervention studies, we categorized 19 288 patients into 4 groups: high-normal hemoglobin (≥14.0 g/dL; n=7555), low-normal hemoglobin (13.0-13.9 g/dL in men and 12.0-13.9 g/dL in women; n=5303), mild anemia (11.0-12.9 g/dL in men and 11.0-11.9 g/dL in women; n=4117), and moderate/severe anemia (<11.0 g/dL; n=2313). Median follow-up duration was 3 years. Low-normal hemoglobin, mild anemia, and moderate/severe anemia correlated with significant excess risk relative to high-normal hemoglobin for GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Arteries Trial) moderate/severe bleeding, with adjusted hazard ratios of 1.22 (95% CI, 1.04-1.44), 1.73 (95% CI, 1.47-2.04), and 2.31 (95% CI, 1.92-2.78), respectively. Moderate/severe anemia also correlated with significant excess risk relative to high-normal hemoglobin for the ischemic composite end point of myocardial infarction/ischemic stroke (adjusted hazard ratio, 1.33; 95% CI, 1.11-1.60), whereas low-normal hemoglobin and mild anemia did not. However, the excess risk of low-normal hemoglobin, mild anemia, and moderate/severe anemia relative to high-normal hemoglobin remained significant for ischemic stroke and for mortality. Conclusions: Decreasing baseline hemoglobin correlated with incrementally higher long-term risk for major bleeding, ischemic stroke, and mortality after percutaneous coronary intervention. Even within normal range, lower baseline hemoglobin level correlated with higher ischemic and bleeding risk