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Wide-field microscopy using a Zeiss Axioskop FS microscope Zeiss, Oberkochen, Germany ; equipped with an intensified CCD camera Stanford Photonics ; as described previously Mackenzie et al., 1996 ; , using a 60 water immersion 0.9 numerical aperture objective Olympus, Tokyo, Japan ; for optical recordings. The camera acquired data at 15 frames per second pixel size 0.2 m ; , and the images were captured to a PC using a frame grabber EPIX, Buffalo Grove, IL ; . BAPTA in the pipette solution was substituted with Fluo-4 0.4 mM ; and mag-fura-2 0.2 0.3 mM ; for Ca 2 imaging. Mag-fura-2, a low-affinity Ca 2 indicator with high fluorescence at basal [Ca 2 ]i at 380 nm excitation Raju et al., 1989 ; was used to resolve the fine processes under resting conditions, and Fluo-4 was used to view local changes in [Ca 2 ]i. For each optical recording trial, we collected 20 sec of Fluo-4 images 300 frames; at 490 nm excitation ; and then switched to 380 nm excitation to collect one averaged 1 sec ; mag-fura-2 image for normalization see below ; . The excitation light was delivered to the microscope using a flexible fiber optic cable coupled to a filter wheel and an HBO 100 W arc lamp. On the emission side we used a Fura Fluo-4 dichroic mirror Chromo Technologies, catalog #74000 ; combined with a 540 40 nm emission filter. For electrophysiological experiments in which relative changes in AMPA receptor-mediated miniature EPSCs AMPAR mEPSCs ; were measured, 0.2 mM BAPTA was included in the pipette solution, and simultaneous Ca 2 imaging was not performed in most experiments ; . In initial experiments we found that BAPTA afforded better recording conditions than the Fluo-4 and allowed us to collect more trials evaluating mEPSC rate after train stimulation. Because BAPTA has a twofold lower Kd 160 vs 345 nM ; than Fluo-4 Molecular Probes, Eugene, OR; data table ; , we used 0.2 mM BAPTA for electrophysiology-only experiments and 0.4 mM Fluo-4 for imaging to match buffer capacity under the two experimental conditions buffer concentration Kd buffer buffer capacity; 1250 BAPTA vs 1160 Fluo-4 ; . Buffer capacity a measure of bound Ca 2 to free Ca 2 at equilibrium ; and the Ca 2 extrusion rate are the primary determinants of Ca 2 clearance Neher and Augustine, 1992; Helmchen and Tank, 2000 ; . To check that the use of BAPTA 0.2 mM ; versus Fluo-4 0.4 mM ; did not affect the relative time course of asynchronous release, we recorded AMPAR-mediated asynchronous mEPSCs in three neurons in which imaging experiments were also performed in the presence of Fluo-4 0.4 mM ; . We then calculated relative changes in whole-cell current variance during the asynchronous phase of release to provide a relative measure of mEPSC rate decay as done for electrophysiological experiments; see Fig. 4 ; . Fitting the fast component of the decay of variance, we observed only a modest difference between cells loaded with Fluo-4 0.4 mM ; or BAPTA 0.2 mM ; : 257 16 and 213 16 msec, respectively. This analysis confirms that our electrophysiological conditions are comparable with those under which imaging experiments were performed. Importantly, in all imaging trials we also recorded the time course of asynchronous NMDAR-dependent synaptic activity and found that it was well correlated with AMPA mEPSC frequency determined from electrophysiological experiments at periods 0.8 18 sec after train stimulation ; . In the extracellular solution, 1 mM D amino adipate D-AA ; , a lowaffinity competitive NMDAR antagonist, was added to block NMDAR activation during train stimulation and to permit rapid NMDAR unblocking after washout. To monitor Ca 2 signals through NMDARs, the extracellular solution without NMDAR antagonists MgCl2 and D-AA free ; was applied using computer-controlled solenoid-driven valves via a glass pipette 200 m tip, inner diameter ; positioned 400 m from a recording cell. Imaging trials were captured at 1 min intervals to reduce synaptic depression and potential toxic effects of NMDAR activation. Fluo-4 and mag-fura-2 were purchased from Molecular Probes. D, LAPV was purchased from Precision Biochemicals Vancouver, British Columbia, Canada ; . D-AA and other chemicals were purchased from Sigma St. Louis, MO ; . Data analysis. Phasic and asynchronous components of release as well as RRP size during 20 Hz stimulation for 0.5 sec were measured as described previously Otsu et al., 2004 ; . Currents were analyzed off-line using programs written in the Interactive Data Language IDL ; Research System, Boulder, CO ; programming language on a Pentium processor-based computer. Spontaneous events mEPSC ; were detected.
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Gardiner HM; Wimalasundera R; Pasquini L; Wawryk S; Ho SY Images in cardiovascular medicine. Pericardiocentesis at 14 weeks: effective treatment of pericardial effusion complicating right ventricular diverticulum. Circulation 112 9 ; e120Gardiner HM; Wimalasundera R; Pasquini L; Wawryk S; Ho SY Pericardiocentesis at 14 weeks - Effective treatment of pericardial effusion complicating right ventricular diverticulum Circulation 112 9 ; E120-E120 Gardiner HM Response of the fetal heart to changes in load: from hyperplasia to heart failure. Heart 91 7 ; 871-873 Gardiner HM Keeping abreast of advances in fetal cardiology. Early Hum Dev Pasquini L; Fichera A; Tan T; Ho SY; Gardiner H Left superior caval vein: a powerful indicator of fetal coarctation. Heart 91 4 ; 539-540 Gardiner HM; Kumar S Fetal cardiac interventions. Clin Obstet Gynecol 48 4 ; 956-963 Gardiner HM; Pasquini L; Wolfenden J; Barlow A; Li W; Kulinskaya E; Henein M Myocardial tissue Doppler and long axis function in the fetal heart. Int J Cardiol Gardiner HM; Pasquini L; Wolfenden J; Kulinskaya E; Li W; Henein MY Increased periconceptual maternal glycosolated haemoglobin in diabetic mothers reduces fetal long axis cardiac function. Heart Gardiner HM; Franklin RC; Daubeney PE; Rigby ML; Kumar S Percutaneous fetal vaIvuloplasty: Four years' experience Circulation 112 17 ; U711-U712 Pasquini L; Tan T; Yen Ho S; Gardiner H The implications for fetal outcome of an abnormal arrangement of the abdominal vessels. Cardiol Young 15 1 ; 35-42 Gardiner HM Progression of fetal heart disease and rationale for fetal intracardiac interventions. Semin Fetal Neonatal Med 10 6 ; 578-585 Main Author Prof Vivette Glover. 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