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The authors examine the role of calcium-activated potassium channels in cardiac development based on a study conducted by researcher S. Karppinen and colleagues. The researchers found that these channels can regulate embryonic pacemaking and action potential configuration. The authors suggest that membrane repolarization and L-type calcium current should be fine-tuned to help potassium channels modulate calcium-dependent hypertrophy.

Stem cells provide broad possibilities in modern science and medicine. This counts not only for investigations of developmental aspects but also for cell-based therapies, pharmacotoxicological testing and improvements in personalized medicine. The recent described techniques of induced pluripotent stem cells, directly induced neural stem cells and directly induced neurons are a major step forward by providing new possibilities for research on neurological diseases. Nevertheless, a variety of questions remain open regarding stem cell-based therapeutic strategies including tumorigenicity and phenotypical stability in the receptor brain. The major hope is that the new stem cell-based neural cell systems will help to understand the pathophysiology of neurodegenerative diseases. The future will show whether and how stem cells will lead to successful restorative therapies and/or to suitable cell models for neurological diseases. [ABSTRACT FROM AUTHOR]

Highlights: [•] Kvβ2 is an interaction partner of ProSAP2/Shank3. [•] Kvβ2 and ProSAP2Shank3 colocalize at the neuronal PSD. [•] The interacting domain of ProSAP2/Shank3 is the PDZ domain. [ABSTRACT FROM AUTHOR]

Objective: The efficacy and safety of atomoxetine, the only licensed non-stimulant pharmacological treatment option for ADHD in Europe, is well investigated in clinical trials, the long-term effects in the developing brain still remain elusive. In vitro studies prove that besides the well-known inhibition of the norepinephrine transporter (NET) atomoxetine acts as a blocker of the N-methyl-D-aspartate (NMDA) receptor. Here we present an in vivo study carried out to investigate atomoxetine’s effect in the maturing rat brain. Methods: Pregnant Crl:SD(CD) rats were treated with atomoxetine (3 mg/kg, i.p.) and sodium chloride (0.9%, i.p.), for the period equivalent to human second to third trimenon of pregnancy. After the end of treatment hippocampus, prefrontal cortex, mesencephalon and striatum from embryos and dams were isolated for analysis of gene expression. Results: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed altered expression of genes of the monoaminergic and glutamatergic system in both embryos and dams. Discussion: This study gives hints that atomoxetine might alter transcriptional regulation of genes of the monoaminergic and glutamatergic system in an age-dependent manner. Conclusion: Atomoxetine alters gene expression in vivo. [ABSTRACT FROM AUTHOR]

Abstract: Abelson interactor protein 1 (Abi-1) localizes to postsynaptic densities (PSDs) of excitatory synapses and was shown to be transported from the PSD to the nucleus and back depending upon synaptic activation. We employed a yeast-two-hybrid screen to search for putative transport molecules. We found Kif26B a member of the Kif family of transport proteins that has not been characterized in the central nervous system as a direct interaction partner of Abi-1. We delineated a proline-rich motif within the cargo-binding domain of Kif26B to be responsible for this protein–protein interaction. Kif26B was able to recruit Abi-1 to the microtubule network and we found that the expression of Kif26B is responsible for the localization of Abi-1 to PSDs in maturing neurons. Taken together we report that Abi-1 is a cargo of Kif26B in primary hippocampal neurons, pointing to a role of this transport molecule in the movement of Abi-1 between different cell compartments. Additionally, we provide the first detailed investigation of Kif26B and its cargo molecules in neuronal cells. [Copyright &y& Elsevier]

Methylphenidate (MPH) is the most common used drug in child and adolescent psychiatry. Despite of this fact, however, little is known about its exact pharmacological mechanisms. Here we investigated the toxic effects of MPH in vitro in human embryonic kidney (HEK-293) cells stably expressing the human dopamine transporter (HEK-hDAT cells) and in cultured rat embryonic (E14.5) mesencephalic cultures. MPH alone (up to 1 mM) affected neither the growth of HEK-hDAT cells nor the survival of dopaminergic (DA) neurons in primary cultures after treatment up to 72 h. No differences in neuronal arborisation or in the density of synapses were detected. 1-methyl-4-phenylpyridinium (MPP+) showed no toxic effect in HEK-293 cells, but had significant toxic effects in HEK-hDAT cells and DA neurons. MPH (1 µM – 1 mM) dose-dependently reduced this cytotoxicity in HEK-hDAT cells and primary mesencephalic DA neurons. The presented results show that application of MPH alone does not have any toxic effect on DA cells in vitro. The neurotoxic effects of MPP+ could be significantly reduced by co-application of MPH, an effect that is most likely explained by MPH blocking the DAT. [ABSTRACT FROM AUTHOR]