Aberrant generation of dentate gyrus granule cells is associated with epileptic susceptibility in p53 conditional knockout mice.

Neuronal apoptosis is a mechanism used to clear the cells of oxidative stress or DNA damage and refine the final number of neurons for a functional neuronal circuit. The tumor suppressor protein p53 is a key regulator of the cell cycle and serves as a checkpoint for eliminating neurons with high DNA damage, hyperproliferative signals or cellular stress. During development, p53 is largely expressed in progenitor cells.

Conditional deletion of KCC2 impairs synaptic plasticity and both spatial and nonspatial memory.

The postsynaptic inhibition through GABA receptors (GABAR) relies on two mechanisms, a shunting effect due to an increase in the postsynaptic membrane conductance and, in mature neurons, a hyperpolarization effect due to an entry of chloride into postsynaptic neurons. The second effect requires the action of the K-Cl cotransporter KCC2 which extrudes Cl from the cell and maintains its cytosolic concentration very low. Neuronal chloride equilibrium seems to be dysregulated in several neurological and psychiatric conditions such as epilepsy, anxiety, schizophrenia, Down syndrome, or Alzheimer's disease.

A TRPM7 mutation linked to familial trigeminal neuralgia: Omega current and hyperexcitability of trigeminal ganglion neurons.

Trigeminal neuralgia (TN) is a unique pain disorder characterized by intense paroxysmal facial pain within areas innervated by the trigeminal nerve. Although most cases of TN are sporadic, familial clusters of TN suggest that genetic factors may contribute to this disorder. Whole-exome sequencing in patients with TN reporting positive family history demonstrated a spectrum of variants of ion channels including TRP channels.

Overexpression of wild-type human amyloid precursor protein alters GABAergic transmission.

The function of the amyloid precursor protein (APP) is not fully understood, but its cleavage product amyloid beta (Aβ) together with neurofibrillary tangles constitute the hallmarks of Alzheimer's disease (AD). Yet, imbalance of excitatory and inhibitory neurotransmission accompanied by loss of synaptic functions, has been reported much earlier and independent of any detectable pathological markers. Recently, soluble APP fragments have been shown to bind to presynaptic GABA receptors (GABARs), subsequently decreasing the probability of neurotransmitter release.

Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells.

Defects in protein reabsorption by the proximal tubule are toxic for epithelial cells in the nephron and may result in nephropathy. In this study, we showed that the ion channel TRPV4 modulated the endocytosis of albumin and low-molecular weight proteins in the proximal tubule. TRPV4 was found at the basolateral side of proximal tubule cells, and its mechanical activation by cell stretching induced Ca entry into the cytosol, which promoted endocytosis.

Role of the TRPC1 Channel in Hippocampal Long-Term Depression and in Spatial Memory Extinction.

Group I metabotropic glutamate receptors (mGluR) are involved in various forms of synaptic plasticity that are believed to underlie declarative memory. We previously showed that mGluR5 specifically activates channels containing TRPC1, an isoform of the canonical family of Transient Receptor Potential channels highly expressed in the CA1-3 regions of the hippocampus. Using a tamoxifen-inducible conditional knockout model, we show here that the acute deletion of the gene alters the extinction of spatial reference memory.

Activation of TRPC1 Channel by Metabotropic Glutamate Receptor mGluR5 Modulates Synaptic Plasticity and Spatial Working Memory.

Group I metabotropic glutamate receptors, in particular mGluR5, have been implicated in various forms of synaptic plasticity that are believed to underlie declarative memory. We observed that mGluR5 specifically activated a channel containing TRPC1, an isoform of the canonical family of transient receptor potential (TRPC) channels highly expressed in CA1-3 regions of the hippocampus. TRPC1 is able to form tetrameric complexes with TRPC4 and/or TRPC5 isoforms.

Effects of genetic deletion of soluble 5'-nucleotidases NT5C1A and NT5C2 on AMPK activation and nucleotide levels in contracting mouse skeletal muscles.

AMP-activated protein kinase (AMPK) plays a key role in energy homeostasis and is activated in response to contraction-induced ATP depletion in skeletal muscle via a rise in intracellular AMP/ADP concentrations. AMP can be deaminated by AMP-deaminase (AMPD) to IMP, which is hydrolyzed to inosine by cytosolic 5'-nucleotidase II (NT5C2). AMP can also be hydrolyzed to adenosine by cytosolic 5'-nucleotidase 1A (NT5C1A).

TRPV4 participates in pressure-induced inhibition of renin secretion by juxtaglomerular cells.

Key Points: Increase in blood pressure in the renal afferent arteriole is known to induce an increase in cytosolic calcium concentration ([Ca ] ) of juxtaglomerular (JG) cells and to result in a decreased secretion of renin. Mechanical stimulation of As4.1 JG cells induces an increase in [Ca ] that is inhibited by HC067047 and RN1734, two inhibitors of TRPV4, or by siRNA-mediated repression of TRPV4.

Sphingosine-1-phosphate-activated TRPC1 channel controls chemotaxis of glioblastoma cells.

TRP channels are involved in the control of a broad range of cellular functions such as cell proliferation and motility. We investigated the gating mechanism of TRPC1 channel and its role in U251 glioblastoma cells migration in response to chemotaxis by platelet-derived growth factor (PDGF). PDGF induced an influx of Ca that was partially inhibited after pretreatment of the cells with SKI-II, a specific inhibitor of sphingosine kinase producing sphingosine-1-P (S1P).

Redundant control of migration and adhesion by ERM proteins in vascular smooth muscle cells.

Ezrin, radixin, and moesin possess a very similar structure with a C-terminal actin-binding domain and a N-terminal FERM interacting domain. They are known to be involved in cytoskeleton organization in several cell types but their function in vascular smooth muscle cells (VSMC) is still unknown. The aim of this study was to investigate the role of ERM proteins in cell migration induced by PDGF, a growth factor involved in pathophysiological processes like angiogenesis or atherosclerosis.

Different effect of Rho kinase inhibition on calcium signaling in rat isolated large and small arteries.

In addition to its role in the regulation of artery contraction, Rho kinase (ROCK) was reported to be involved in the cytosolic calcium response to vasoconstrictor agonists in rat aorta and superior mesenteric artery (SMA). However, it remains to be determined whether ROCK also contributes to calcium signaling in resistance arteries, which play a major role in blood pressure regulation. The investigation of the effect of ROCK inhibition on the calcium and contractile responses of rat resistance mesenteric artery (RMA), in comparison with aorta and SMA, indicated that the calcium response to noradrenaline was inhibited by the ROCK inhibitor Y-27632 in aorta and SMA but not in RMA.

Rho kinase regulation of vasopressin-induced calcium entry in vascular smooth muscle cell: comparison between rat isolated aorta and cultured aortic cells.

In addition to its role in artery contraction, Rho kinase (ROCK) is reported to be involved in the Ca(2+) response to vasoconstrictor agonist in rat aorta. However the signaling pathway mediated by ROCK had not been investigated so far and it was not known whether ROCK also contributed to Ca(2+) signaling in cultured vascular smooth muscle cells (VSMC), which undergo profound phenotypic changes. Our results showed that in VSMC, ROCK inhibition by Y-27632 or H-1152 had no effect on the Ca(2+) response to vasopressin, while in aorta the vasopressin-induced Ca(2+) entry was significantly decreased.

EBP50 is involved in the regulation of vascular smooth muscle cell migration and cytokinesis.

Ezrin, Radixin, Moesin binding phosphoprotein 50 (EBP50) is a scaffold protein that possesses two PDZ interacting domains. We have shown that, in isolated artery stimulated with noradrenaline, EBP50 interacts with several elements of the cytoskeleton. However, the contribution of EBP50 to the organization of the cytoskeleton is unknown.