Cell-based potassium ion channel screening using the FluxOR assay.

FluxOR technology is a cell-based assay used for high-throughput screening measurements of potassium channel activity. Using thallium influx as a surrogate indicator of potassium ion channel activity, the FluxOR Potassium Ion Channel Assay is based on the activation of a novel fluorescent dye. This indicator reports channel activity with a large fluorogenic response and is proportional to the number of open potassium channels on the cell, making it extremely useful for studying K(+) channel targets.

Dendritic calcium channels and their activation by synaptic signals in auditory coincidence detector neurons.

The avian nucleus laminaris (NL) encodes the azimuthal location of low-frequency sound sources by detecting the coincidence of binaural signals. Accurate coincidence detection requires precise developmental regulation of the lengths of the fine, bitufted dendrites that characterize neurons in NL. Such regulation has been suggested to be driven by local, synaptically mediated, dendritic signals such as Ca(2+).

G-protein-coupled receptor pharmacology: examining the edges between theory and proof.

Over the past year, several salubrious concepts in the field of G-protein-coupled receptors (GPCRs) have been brought to the forefront of GPCR research, and theoretical models that describe their activation continue to be amended to accommodate new experimental data. Pharmacologists have traditionally divided ligands into agonists, which stimulate receptors, and antagonists, which block receptor activation. More recently, however, scientists have come to realize that GPCRs can also exhibit basal activity, and with this knowledge they have come to the understanding that many drugs previously classified as neutral antagonists, actually demonstrate 'negative efficacies'.

Presynaptic G-protein-coupled receptors regulate synaptic cleft glutamate via transient vesicle fusion.

When synaptic vesicles fuse with the plasma membrane, they may completely collapse or fuse transiently. Transiently fusing vesicles remain structurally intact and therefore have been proposed to represent a form of rapid vesicle recycling. However, the impact of a transient synaptic vesicle fusion event on neurotransmitter release, and therefore on synaptic transmission, has yet to be determined.

G protein betagamma-subunits activated by serotonin mediate presynaptic inhibition by regulating vesicle fusion properties.

Neurotransmitters are thought to be released as quanta, where synaptic vesicles deliver packets of neurotransmitter to the synaptic cleft by fusion with the plasma membrane. However, synaptic vesicles may undergo incomplete fusion. We provide evidence that G protein-coupled receptors inhibit release by causing such incomplete fusion.

Gbetagamma acts at the C terminus of SNAP-25 to mediate presynaptic inhibition.

Presynaptic inhibition mediated by G protein-coupled receptors may involve a direct interaction between G proteins and the vesicle fusion machinery. The molecular target of this pathway is unknown. We demonstrate that Gbetagamma-mediated presynaptic inhibition in lamprey central synapses occurs downstream from voltage-gated Ca(2+) channels.

G protein betagamma directly regulates SNARE protein fusion machinery for secretory granule exocytosis.

The activation of G protein-coupled receptors (GPCRs) can result in an inhibition of Ca(2+)-dependent hormone and neurotransmitter secretion. This has been attributed in part to G protein inhibition of Ca(2+) influx. However, a frequently dominant inhibitory effect, of unknown mechanism, also occurs distal to Ca(2+) entry.