Involvement of NMDAR2A tyrosine phosphorylation in depression‐related behaviour

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/1/embj2009300-sup-0001.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/2/embj2009300.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/102200/3/embj2009300-sup-0003.pd

Coronary artery vasospasms in a microminipig occurred after placing an ameroid constrictor

A 12-month-old microminipig, weighing 12.6 kg, showed 3 repeated episodes of transient ST-segment elevation in 24 hr Holter electrocardiogram after placing an ameroid constrictor around the left anterior descending coronary artery. Ventricular fibrillation was noticed just after the cessation of the 24 hr Holter-electrocardiogram recording. Direct current defibrillations and cardiopulmonary resuscitation were performed; however, they were unsuccessful, leading to the animal’s death. Its heart was excised for macroscopic analysis, which indicated that lumen of the ameroid constrictor was not narrowed and that there was no dissection, embolus or thrombus in the coronary arteries, indirectly suggesting that coronary artery vasospasm may have caused the ischemic attacks. Thus, microminipig may possess some potential to have coronary vasospasm

Analysis of torsadogenic and pharmacokinetic profile of E-4031 in dogs bridging the gap of information between in vitro proarrhythmia assay and clinical observation in human subjects

We analyzed torsadogenic and pharmacokinetic profile of E-4031 using chronic atrioventricular block dogs. E-4031 in intravenous doses of 0.03, 0.1 and 0.3 mg/kg over 10 min prolonged QT/QTc, and increased short-term variability of QT in a dose-related manner (n = 4), resulting in onset of torsade de pointes in 1 animal after the middle dose and 4 animals after the high dose, while it attained peak plasma concentrations of 16.5, 60.5 and 182.5 ng/mL at 10 min after their start of administration, respectively (n = 2). These results bridge the gap of information between in vitro proarrhythmia assay and clinical observation in human subjects. Keywords: E-4031, Torsade de pointes, CiP

Application of human induced pluripotent stem cell-derived cardiomyocytes sheets with microelectrode array system to estimate antiarrhythmic properties of multi-ion channel blockers

We examined electrophysiological indices of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) sheets in order to quantitatively estimate Na+, K+ and Ca2+ channel blocking actions of bepridil and amiodarone using microelectrode array system in comparison with that of E-4031. We analyzed the field potential duration, effective refractory period, current threshold and conduction property using a programmed electrical stimulation protocol to obtain the post repolarization refractoriness and coefficient a of the relationship between the pacing cycle length and field potential duration. Electropharmacological profile of each drug was successfully characterized; namely, 1) the changes in the current threshold and conduction property provided basic information of Na+ channel blocking kinetics, 2) the relationship between pacing cycle length and field potential duration reflected drug-induced inhibition of human ether-à-go-go-related gene (hERG) K+ channel, 3) the post repolarization refractoriness indicated the relative contribution of these drugs to Na+ and K+ channel blockade, and 4) L-type Ca2+ channel blocking action was more obvious in the field potential waveform of the hiPSC-CMs sheets than that expected in the electrocardiogram in humans. Thus, this information may help to better utilize the hiPSC-CMs sheets for grasping the properties and net effects of drug-induced Na+, Ca2+ and K+ channel blockade. Keywords: Human induced pluripotent stem cell-derived cardiomyocytes, Post repolarization refractoriness, Multichannel blocker, Antiarrhythmic propert