The Ca(V) 1.2 Ca(2+) channel is expressed in sarcolemma of type I and IIa myofibers of adult skeletal muscle.

Although Ca(2+)-dependent signaling pathways are important for skeletal muscle plasticity, the sources of Ca(2+) that activate these signaling pathways are not completely understood. Influx of Ca(2+) through surface membrane Ca(2+) channels may activate these pathways. We examined expression of two L-type Ca(2+) channels in adult skeletal muscle, the Ca(V) 1.1 and Ca(V) 1.2, with isoform-specific antibodies in Western blots and immunocytochemistry assays. Consistent with a large body of work, expression of the Ca(V) 1.1 was restricted to skeletal muscle where it was expressed in T-tubules. Ca(V) 1.2 was also expressed in skeletal muscle, in the sarcolemma of type I and IIa myofibers. Exercise-induced alterations in muscle fiber types cause a concomitant increase in the number of both Ca(V) 1.2 and type IIa-positive fibers. Taken together, these data suggest that the Ca(V) 1.2 Ca(2+) channel is expressed in adult skeletal muscle in a fiber type-specific manner, which may help to maintain oxidative muscle phenotype.

Development of functional neurons from postnatal stem cells in vitro.

In order for stem cells to fulfill their clinical promise, we must understand their developmental transitions and it must be possible to control the differentiation of stem cells into specific cell fates. To understand the mechanism of the sequential restriction and multipotency of stem cells, we have established culture conditions that allow the differentiation of multipotential neural stem cells from postnatal stem cells. We used immunocytochemistry, fluorescence microscopy, and calcium imaging to demonstrate that progeny of adult rat neural stem cells develop into functional neurons that release excitatory neurotransmitters. We also found that the nontoxic heavy chain fragment of tetanus toxin, a toxin that targets neurons with high specificity, retained the specificity toward neural stem cell-derived neurons. These studies show that neural stem cells derived from adult tissues retain the potential to differentiate into functional neurons with morphological and functional properties of mature central nervous system neurons.

A mesoporous silica nanosphere-based carrier system with chemically removable CdS nanoparticle caps for stimuli-responsive controlled release of neurotransmitters and drug molecules.

An MCM-41 type mesoporous silica nanosphere-based (MSN) controlled-release delivery system has been synthesized and characterized using surface-derivatized cadmium sulfide (CdS) nanocrystals as chemically removable caps to encapsulate several pharmaceutical drug molecules and neurotransmitters inside the organically functionalized MSN mesoporous framework. We studied the stimuli-responsive release profiles of vancomycin- and adenosine triphosphate (ATP)-loaded MSN delivery systems by using disulfide bond-reducing molecules, such as dithiothreitol (DTT) and mercaptoethanol (ME), as release triggers. The biocompatibility and delivery efficiency of the MSN system with neuroglial cells (astrocytes) in vitro were demonstrated. In contrast to many current delivery systems, the molecules of interest were encapsulated inside the porous framework of the MSN not by adsorption or sol-gel types of entrapment but by capping the openings of the mesoporous channels with size-defined CdS nanoparticles to physically block the drugs/neurotransmitters of certain sizes from leaching out. We envision that this new MSN system could play a significant role in developing new generations of site-selective, controlled-release delivery nanodevices.