We have investigated the mechanisms of blockade of calcium channel current by the dihydropyridines, e.g. nisoldipine, nitrendipine, and nicardipine. Membrane current was recorded in isolated calf Purkinje fibers using a two-microelectrode voltage-clamp technique, and voltage protocols were designed to identify voltage- and use-dependent block by these compounds systematically. Our results show ...

Research in the epilepsy field is moving from a primary focus on controlling seizures to addressing disease pathophysiology. This requires the adoption of resource- and time-consuming animal models of chronic epilepsy which are no longer able to sustain the testing of even moderate numbers of compounds. Therefore, new in vitro functional assays of epilepsy are needed that are able to provide a ...

The therapeutic agents flunarizine and lomerizine exhibit inhibitory activities against a variety of ion channels and neurotransmitter receptors. We have optimized their scaffolds to obtain more selective N-type calcium channel blockers. During this optimization, we discovered NP118809 and NP078585, two potent N-type calcium channel blockers which have good selectivity over L-type calcium chann...

It has been thought that phosphorus in biominerals made of amorphous calcium carbonate (ACC) might be related to ACC formation, but no such phosphorus-containing compounds have ever been identified. Crustaceans use ACC biominerals in exoskeleton and gastroliths so that they will have easy access to calcium carbonate inside the body before and after molting. We have identified phosphoenolpyruvat...

Calcium has been implicated as a factor regulating the motility and proliferation of cultured fibroblasts. Since little is known about how the intracellular concentration of calcium is regulated in cultured fibroblasts, we have characterized the microsomal calcium transport activity of Balb/c 3T3 cells, an established line of mouse fibroblasts. Calcium uptake by the microsomal fraction is enhan...

While arsenic compounds are known as environmental toxicants (especially in drinking water) and as carcinogens, some arsenic compounds, like arsenic trioxide (As2O3), are clinically used in humans to treat some forms of cancer (e.g. leukemia). Although arsenic compounds have been studied intensively, their interactions with living cells are still not fully elucidated. We have previously propose...

Platinum compounds cause significant clinical neurotoxicity. Several studies highlight neurological complications especially in paediatric oncology patients with Central Nervous System (CNS) and non-CNS malignancies. To understand the toxicity mechanisms of platinum drugs at cellular and molecular levels in the immature brain, which appears more vulnerable to injury than in the adult one, we co...

The following review examines the role of calcium in promoting the in vitro and in vivo activation of transglutaminases in neurodegenerative disorders. Diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease exhibit increased transglutaminase activity and rises in intracellular calcium concentrations, which may be related. The aberrant activation of transglutaminase b...

Calcimimetic agents are small organic molecules that act as allosteric activators of the calcium sensing receptor (CaSR) in the parathyroid glands and other tissues. They lower the threshold for CaSR activation by extracellular calcium ions and diminish parathyroid hormone (PTH) release from parathyroid cells. By targeting the molecular mechanism that modulates PTH secretion on a minute-to-minu...

The rodent vomeronasal organ plays an important role in many social behaviors. Using the calcium imaging technique with the dye fluo-4 we measured intracellular calcium concentration changes induced by the application of sulfated steroids to neurons isolated from the vomeronasal organ of female mice. We found that a mix of 10 sulfated steroids from the androgen, estrogen, pregnanolone, and gluc...