Tonic GABAA conductance bidirectionally controls interneuron firing pattern and synchronization in the CA3 hippocampal network.

The spiking output of interneurons is key for rhythm generation in the brain. However, what controls interneuronal firing remains incompletely understood. Here we combine dynamic clamp experiments with neural network simulations to understand how tonic GABAA conductance regulates the firing pattern of CA3 interneurons.

TRPV1 mediates histamine-induced itching via the activation of phospholipase A2 and 12-lipoxygenase.

Histamine provokes itching and is a major skin disease complaint. Histamine is known to excite a subset of sensory neurons, predominantly C-fibers. Although histamine is pruritogenic, its signaling pathways that excite sensory neurons have not been identified.

Novel potent antagonists of transient receptor potential channel, vanilloid subfamily member 1: structure-activity relationship of 1,3-diarylalkyl thioureas possessing new vanilloid equivalents.

Recently, 1,3-diarylalkyl thioureas have merged as one of the promising nonvanilloid TRPV1 antagonists possessing excellent therapeutic potential in pain regulation. In this paper, the full structure-activity relationship for TRPV1 antagonism of a novel series of 1,3-diarylalky thioureas is reported. Exploration of the structure-activity relationship, by systemically modulating three essential pharmacophoric regions, led to six examples of 1,3-dibenzyl thioureas, which exhibit Ca(2+) uptake inhibition in rat DRG neuron with IC(50) between 10 and 100 nM.

Novel non-vanilloid VR1 antagonist of high analgesic effects and its structural requirement for VR1 antagonistic effects.

A novel non-vanilloid VR1 antagonist consisting of a new vanilloid equivalent exhibits excellent analgesic effects as well as highly potent antagonistic activities in both capsaicin single channel and calcium uptake assays. In addition, the structural requirement for the vanilloid equivalent of the potent VR1 antagonist has also been elucidated.

Phosphorylation of vanilloid receptor 1 by Ca2+/calmodulin-dependent kinase II regulates its vanilloid binding.

Vanilloid receptor 1 (VR1), a capsaicin receptor, is known to play a major role in mediating inflammatory thermal nociception. Although the physiological role and biophysical properties of VR1 are known, the mechanism of its activation by ligands is poorly understood. Here we show that VR1 must be phosphorylated by Ca2+-calmodulin dependent kinase II (CaMKII) before its activation by capsaicin.

Calcium-activated cationic channel in rat sensory neurons.

Ion channels in sensory neurons are molecular sensors that detect external stimuli and transduce them to neuronal signals. Although Ca2+-activated nonselective cation (CAN) channels were found in many cell types, CAN channels in mammalian sensory neurons are not yet identified. In the present study, we describe an ion channel that is activated by intracellular Ca2+ in cultured rat sensory neurons.