Interplay between ER Ca2+ uptake and release fluxes in neurons and its impact on [Ca2+] dynamics

In neurons, depolarizing stimuli open voltage-gated Ca2+ channels, leading to Ca2+ entry and a rise in the cytoplasmic free Ca2+ concentration ([Ca2+]i). While such [Ca2+]i elevations are initiated by Ca2+ entry, they are also influenced by Ca2+ transporting organelles such as mitochondria and the endoplasmic reticulum (ER). This review summarizes contributions from the ER to depolarization-evoked [Ca2+]i responses in sympathetic neurons. As in other neurons, ER Ca2+ uptake depends on SERCAs, while passive Ca2+ release depends on ryanodine receptors (RyRs). RyRs are Ca2+ permeable channels that open in response to increases in [Ca2+]i, thereby permitting [Ca2+]i elevations to trigger Ca2+ release through Ca2+-induced Ca2+ release (CICR). However, whether this leads to net Ca2+ release from the ER critically depends upon the relative rates of Ca2+ uptake and release. We found that when RyRs are sensitized with caffeine, small evoked [Ca2+]i elevations do trigger net Ca2+ release, but in the absence of caffeine, net Ca2+ uptake occurs, indicating that Ca2+ uptake is stronger than Ca2+ release under these conditions. Nevertheless, by increasing ER Ca2+ permeability, RyRs reduce the strength of Ca2+ buffering by the ER in a [Ca2+]I-dependent manner, providing a novel mechanism for [Ca2+]i response acceleration. Analysis of the underlying Ca2+ fluxes provides an explanation of this and two other modes of CICR that are revealed as [Ca2+]i elevations become progressively larger.

Effects of hypothyroidism and undernourishment on nuclear-cytoplasmic transport "in vitro"-of cerebral RNA

Efecto del hipotiroidismo y la malnutrición sobre el transporte núcelocitoplasmático de ARN "in vitro". La tiroidectomía neonatal produce en la rata de 10 días de edad modificaciones en la actividad específica del ARN "de marcación rápida", tanto a nivel nuclear como microsomal. La radiactividad del ARN ribosomal, cuya síntesis nuclear no es afectada por el hipotiroidismo, se ve disminuida a nivel microsomal, indicando retraso en el transporte a través de la membrana nucelar. La salida del ARN "de marcación rápida" desde el núcleo no se modifica bajo estas mismas condiciones. La mala nutrición produce cambios similares a los observados en el hipotiroidismo, excepto que la malnutrición, además, disminuye la liberación nuclear de mARN. Alteraciones a nivel de los factores citosólicos parecen ser la causa de la menor liberación nuclear del ARN ribosomal de cerebro de rata hipotiroidea, mientras que cambios en mecanismos intranucleares aún no conocidos serían los responsables de las modificaciones en el transporte de ARN ribosomal de cerebro de rata malnutrida