Acute simvastatin inhibits K-ATP channels of porcine coronary artery myocytes

Background: Statins (3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors) consumption provides beneficial effects on cardiovascular systems. However, effects of statins on vascular KATP channel gatings are unknown.\ud \ud Methods: Pig left anterior descending coronary artery and human left internal mammary artery were isolated and endothelium-denuded for tension measurements and Western immunoblots. Enzymatically-dissociated/cultured arterial myocytes were used for patch-clamp electrophysiological studies and for [Ca²⁺]ᵢ, [ATP]ᵢ and [glucose](o) uptake measurements.\ud \ud Results: The cromakalim (10 nM to 10 μM)- and pinacidil (10 nM to 10 μM)-induced concentration-dependent relaxation of porcine coronary artery was inhibited by simvastatin (3 and 10 μM). Simvastatin (1, 3 and 10 μM) suppressed (in okadaic acid (10 nM)-sensitive manner) cromakalim (10 mM)-and pinacidil (10 μM)-mediated opening of whole-cell K-ATP channels of arterial myocytes. Simvastatin (10 mu M) and AICAR (1 mM) elicited a time-dependent, compound C (1 μM)-sensitive [H-3]-2-deoxy- glucose uptake and an increase in [ATP]ᵢ levels. A time (2-30 min)- and concentration (0.1-10 μM)-dependent increase by simvastatin of p-AMPKα-Thr¹⁷² and p-PP2A-Tyr³⁰⁷ expression was observed. The enhanced p-AMPK alpha-Thr¹⁷² expression was inhibited by compound C, ryanodine (100 μM) and KN93 (10 μM). Simvastatin-induced p-PP2A-Tyr³⁰⁷ expression was suppressed by okadaic acid, compound C, ryanodine, KN93, phloridzin (1 mM), ouabain (10 μM), and in [glucose](o)-free or [Na+](o)-free conditions.\ud \ud Conclusions: Simvastatin causes ryanodine-sensitive Ca²⁺ release which is important for AMPKα-Thr¹⁷² phosphorylation via Ca²⁺/CaMK II.AMPKα-Thr¹⁷² phosphorylation causes [glucose](o) uptake (and an [ATP]ᵢ increase), closure of K-ATP channels, and phosphorylation of AMPK alpha-Thr¹⁷² and PP2A-Tyr³⁰⁷ resulted. Phosphorylation of PP2A-Tyr³⁰⁷ occurs at a site downstream of AMPKα-Thr¹⁷² phosphorylation

Neandertal spatial patterns and occupation dynamics: a regional focus on the central region in Mediterranean Iberia

En el siguiente trabajo se estudian varios conjuntos pertenecientes al Paleolítico medio procedentes del mediterráneo peninsular ibérico con el objetivo de examinar los patrones de ocupación y las estrategias de gestión del territorio. Se presta especial atención al abastecimiento de las materias primas y los comportamientos tecnológicos, los datos procedentes de la fauna y los análisis microespaciales. La variabilidad en los tipos de ocupación de los distintos conjuntos nos muestra una gran diversidad y una multitud de factores, aunque no parece tener una sola explicación cultural, funcional, temporal o ambiental. Más bien son explicaciones que responden a una amplia variabilidad en los comportamientos técnicos observados y que se explican en función de las propias necesidades de las poblaciones dentro de cada región. Los resultados obtenidos nos permiten analizar los datos y compararlos en el contexto del sudoeste de Europa de cara a elaborar un primer enfoque de las estrategias de subsistencia de los neandertales y su movilidad en una región hasta ahora poco conocida desde este punto de vista.HAR2017-85,153-P/MICINNPROMETEO/2017/060HAR2016-76,760-C3-1-P/MICINNThis paper focuses on the study of some Middle Palaeolithic assemblages from Mediterranean Iberia to examine Neanderthal occupation patterns and territory management strategies, paying special attention to raw material procurement and technological behaviours, zooarchaeological data and microspatial patterning. The site occupation types are variable, and some of the results may have more importance than is immediately apparent, but there does not seem to be a single cultural, functional, temporal or environmental explanation. Rather, the wide variability in the technical behaviours observed can be explained with reference to the particular requirements of the populations in each specific region. The results obtained allow us to interrogate the data and, drawing comparisons with the southwest European context, establish an initial approach to Neanderthal subsistence strategies and mobility in a region so far little known in this regard