Exhumation, doming and slab retreat in the Betic Cordillera (SE Spain): in situ 40Ar/39Ar ages and P­T­d­t paths for the Nevado-Filabride complex

International audienceThe combination of metamorphic petrology tools and in situ laser 40Ar/39Ar dating on phengite (linking time of growth, compositions and PT conditions) enables us to identify a detailed PTdt path for the still debated tectonometamorphic evolution of the Nevado-Filabride complex and infer new geodynamic-scale constraints. Our data show an isothermal decompression (at 550 °C) from 20 kbar for the Bédar-Macael unit and 14 kbar for the Calar Alto unit down to c. 34 kbar for both units at 2.8 mm year1. At 2218 Ma, this first part of the exhumation is followed by a final exhumation at 0.6 mm year1 along a high-temperature low-pressure (HTLP) gradient of c. 60 °C km1. The age of the peak of pressure is not precisely known but it is shown that it is around 30 Ma and possibly older, which is at variance with recent models suggesting a younger age for high-pressure (HP) metamorphism. Most of the exhumation is related to late-orogenic extension from c. 30 to 2218 Ma. Thus the formation of the main ductile extensional shear zone, the Filabres Shear Zone (FSZ), occurred at 2218 Ma and is clearly associated with a top-to-the-west shear sense once the FSZ is well localized. The transition from ductile to brittle then occurred at c. 14 Ma. The final exhumation, accommodated by brittle deformation, occurred from c. 14 to 9 Ma and was accompanied, from 12 to 8 Ma, by the formation of nearby extensional basins. The duration of the extensional process is c. 20 Myr which argues in favour of a progressive slab retreat from c. 30 to 9 Ma. The change in the shape of the PT path at 2218 Ma together with strain localization along the main top-to-the-west shear zone suggests that this date corresponds to a change in the direction of slab retreat from southwards to westwards

A new role of AMP-activated protein kinase in regulating proliferation of mesenchymal stem cells

Purpose: Natriuretic peptides (NPs) administered during early reperfusion are protective in models of myocardial infarction. A previous study examining the endogenous components of B-type natriuretic peptide (BNP) protection of reperfused myocardium, implicated both sarcolemmal (s) KATP and mitochondrial (m) KATP channels. The indirect evidence characterising the relationship between BNP signalling and KATP was obtained using sulphonylurea receptor inhibitors in a rat isolated heart model of ischaemia-reperfusion injury. Here we seek to further examine the relationship between NPs and sKATP openings using single channel electrophysiology. Given our previous findings and the overarching consensus that cardioprotective autacoids open KATP channels, it was hypothesised that NPs elicit sKATP opening. Methods: Cardiomyocyte isolation. Left ventricular cardiomyocytes were isolated from male Sprague-Dawley rat hearts subjected to enzymatic digestion with Liberase Blendzyme DL. Cardiomyocytes were cultured overnight in Medium 199, prior to patch clamp. Single channel patch clamp. Single channel recordings at room temperature (22°C) were made from cell attached patches bathed in Na+ Locke, pH 7.2. The recording pipette contained high KCl (140 mM), pH 7.2. Recordings (45 sec) were made over a range of patch potentials (0, -30, -60, -90, -120 mV), in the absence (control) and in the presence of bath applied BNP (10, 100 nM and 1 µM), pinacidil (200 µM) or pinacidil vehicle (DMSO, 0.25%). Recordings were also made with BNP and pinacidil applied concomitantly. Data are mean ± S.E.M. Results: The current voltage relationship of sKATP under control conditions was linear at –ve patch potentials, the mean conductance being 52.9 ± 1.8 pS (n = 18 hearts, n = 35 cells). Pinacidil caused a four fold increase in sKATP open probability compared to control. Mean channel conductance in the presence of pinacidil was 59.9 ± 1.9 pS (n = 16 hearts, n = 44 cells). Interestingly BNP at all concentrations had negligible effects on sKATP open probability and unitary conductance. However, BNP at all concentrations and patch potentials inhibited pinacidil induced sKATP openings, restoring channel open probability to baseline. Conclusion: These data illustrate the inhibitory effect of NP signalling on sKATP function in the cardiomyocyte under normoxia. They are concordant with the inhibitory effect of atrial NP on KATP in the pancreatic beta cell, but are in apparent conflict with the current cardioprotection paradigm. However, differential effects on sKATP and mKATP and the effects of hypoxia-reoxygenation require further exploration

Potentiation effect of the AMPK activator A-769662 on cardiac myocytes metabolism and survival

Abstract 286 van Poster session 2 Frontiers in CardioVascular Biology, London 30th March – 1st April 2012 Second Congress of the ESC Council on Basic Cardiovascular Science