Novel wasp toxin discriminates between neuronal and cardiac sodium channels

Pompilidotoxins (PMTXs), derived from the venom of solitary wasp has been known to facilitate synaptic transmission in the lobster neuromuscular junction, and a recent further study from rat trigeminal neurons revealed that the toxin slows Na+ channel inactivation without modifying activation process. Here we report that beta -PMTX modifies rat brain type II Na+ channel alpha -subunit (rBII) expressed in human embryonic kidney cells but fails to act on the rat heart alpha -subunit (rH1) at similar concentrations. We constructed a series of chimeric mutants of rBII and rH1 Na+ channels and compared modification of the steady-state Na+ currents by beta -PMTX. We found that a difference in a single amino acid between Glu-1616 in rBII and Gln-1615 in rH1 at the extracellular loop of D4S3-S4 is crucial for the action of beta -PMTX. PMTXs, which are small peptides with 13 amino acids, would be a potential tool for exploring a new functional moiety of Na+ channels.

Anxiogenic-like effects induced by NMDA receptor activation are prevented by inhibition of neuronal nitric oxide synthase in the periaqueductal gray in mice

Glutamate-NMDA (N-methyl-D-aspartate) receptor activation within the periaqueductal gray (PAG) leads to antinociceptive, autonomic and behavioral responses characterized as the fear reaction. We have recently demonstrated that the vigorous defensive-like behaviors (e.g. jumping and running) and antinociception induced by intra-PAG injection of N-methyl-D-aspartate (NMDA) were completely blocked by prior infusion of N(omega)-propyl-L-arginine (NPLA), a specific neuronal nitric oxide synthesis (nNOS) enzyme inhibitor, into the same midbrain structure. It remains unclear however, whether the inhibition of nNOS within the mouse PAG changes the anxiety-like behavior per se or the effects of the inhibition of nNOS depend on the suppression of downstream of glutamate-NMDA receptor activation. This study investigated whether intra-PAG infusion of NPLA (i) attenuates anxiety in the elevated plus-maze (EPM) and (ii) antagonizes the anxiogenic-like effects induced by intra-PAG injection of NMDA. Test sessions were videotaped and subsequently scored for conventional indices of anxiety (percentage of open arm entries and percentage of open arm time) and locomotor activity (closed arm entries). Results showed that intra-PAG infusions of NPLA (0.2, 0.4 or 0.8 nmol/0.1 mu l) did not alter significantly any behavioral response in the EPM when compared to control group (Experiment 1). Intra-PAG infusion of NMDA (0 and 0.02 nmol/0.1 mu l; a dose that does not provoke vigorous defensive behaviors per se in mice) significantly reduced open arm exploration, confirming an anxiogenic-like effect (Experiment 2). When injected into the PAG 10 min prior local NMDA injection (0.02 nmol/0.1 mu l), NPLA (0.4 nmol/0.1 mu l) was able to revert the anxiogenic-like effect of glutamate-NMDA receptor activation. Neither intra-PAG infusion of NMDA nor NPLA altered closed arm entries, a widely used measure of locomotor activity in the EPM. These results suggest that intra-PAG nitric oxide synthesis does not play a role on anxiety-like behavior elicited during EPM exposure; however its synthesis is important for the proaversive effects produced by activation of glutamate-NMDA receptors located within this limbic midbrain structure. (C) 2008 Elsevier B.V. All rights reserved.

Astrocytes and human cognition: Modeling information integration and modulation of neuronal activity

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Coherent atomic oscillations and resonances between coupled Bose-Einstein condensates with time-dependent trapping potential

The atomic tunneling between two tunnel-coupled Bose-Einstein condensates (BECs) in a double-well time-dependent trap was studied. For the slowly varying trap, synchronization of oscillations of the trap with oscillations of the relative population was predicted. Using the Melnikov approach, the appearance of the chaotic oscillations in the tunneling phenomena between the condensates was confirmed.

New CP violation in neutrino oscillations

Measurements of CP-violating observables in neutrino oscillation experiments have been studied in the literature as a way to determine the CP-violating phase in the mixing matrix for leptons. Here we show that such observables also probe new neutrino interactions in the production or detection processes. Genuine CP violation and fake CP violation due to matter effects are sensitive to the imaginary and real parts of new couplings. The dependence of the CP asymmetry on the source-detector distance is different from the standard one and, in particular, enhanced at short distances. We estimate that future neutrino factories will be able to probe in this way new interactions that are up to four orders of magnitude weaker than the weak interactions. We discuss the possible implications for models of new physics. ©2001 The American Physical Society.

Sensitivity of AMPA receptor channel to calcium oscillations: A computational study

We used a computational model of biochemical pathways that are involved in the phosphorylation/dephosphorylation of AMPA receptor to study the receptor responses to calcium oscillations. In the model, the biochemical pathways are assumed to be located immediately under the postsynaptic membrane and we included three states of AMPA receptor: dephosphorylated, and phosphorylated in one or in two sites. To characterize the effects of calcium oscillations on the AMPA receptor, we exposed the model to stimuli with three varying parameters, namely frequency, number of pulses and calcium spike duration. Our model showed sensitivity to all of these three parameters. © 2002 Elsevier Science B.V. All rights reserved.

Endothelial and neuronal nitric oxide synthase inhibitors influences angiotensin II pressor effect in central nervous system

The present study investigated the central role of angiotensin II and nitric oxide on arterial blood pressure (MAP) in rats. Losartan and PD123349 AT 1 and AT 2 (selective no peptides antagonists angiotensin receptors), as well as FK 409 (a nitric oxide donor), N W-nitro-L-arginine methyl ester (L-NAME) a constituve nitric oxide synthase inhibitor endothelial (eNOSI) and 7-nitroindazol (7NI) a specific neuronal nitric oxide synthase inhibitor (nNOSI) were used. Holtzman strain, (Rattus norvergicus) weighting 200-250 g were anesthetized with zoletil 50 mg kg -1 (tiletamine chloridrate 125 mg and zolazepan chloridrate 125 mg) into quadriceps muscle anda stainless steel cannula was stereotaxically implanted into their Lateral Ventricle (LV). Controls were injected with a 0.5 μl volume of 0.15 M NaCl. Angiotensin II injected into LV increased MAP (19±3 vs. control 3±1 mm Hg), which is potentiated by prior injection of L-NAME in the same site 26±2 mm Hg. 7NI injected prior to ANG II into LV also potentiated the pressor effect of ANG II but with a higher intensity than L-NAME 32±3 mm Hg. FK 409 inhibited the pressor effect of ANG II (6±1 mm Hg). Losartan injected into LV before ANG II influences the pressor effect of ANG II (8±1 mm Hg). The PD 123319 decreased the pressor effects of ANG II (16±1 mm Hg). Losartan injected simultaneously with FK 409 blocked the pressor effect of ANG II (3±1 mm Hg). L-NAME produced an increase in the pressor effect of ANG II, may be due to local vasoconstriction and all at once by neuronal NOS inhibition but the main effect is of the 7-NIT an specific nNOS inhibitor. The AT 1 antagonist receptors improve basal nitric oxide (NO) production and release. These data suggest the involvement of constitutive and neuronal NOS in the control of arterial blood pressure induced by ANG II centrally, evolving AT 1 receptor-mediated vasoconstriction and AT 2 receptor-mediated vasodilatation. These results were confirmed by the experiment using FK 409. © 2006 Asian Network for Scientific Information.

The influence of the flame structure on the combustion oscillations in a cylindrical chamber

An experimental study has been conducted with the objective of investigating the effects of the flame structure in the combustion oscillation conditions into a laboratorial scale cylindrical chamber. The experiments were conducted in a water-jacketed 1-m long by 25-cm internal diameter stainless steel vertical tube. The combustor operated with liquefied petroleum gas (LPG) in both oscillatory and non oscillatory conditions, under the same input conditions. Part of the reactant mixture was excited acoustically, before the burner exit, by a speaker positioned strategically. The burner was aligned with the chamber longitudinal axis and positioned at its bottom. The experiments were conducted for 0.16 g/s of LPG burning in stoichiometric equivalence ratio. To analyze the flame structure the image tomographic reconstruction process were used, and the resultant images were associated to the oscillatory conditions (frequency and amplitude) into the combustion chamber. The main conclusions were: 1) when the flame premixed condition increase, for example 60% of the total air flow rate is premixed with LPG, the region of intense energy released is close to burner exit and strong amplitudes of oscillation (close to 50 mbar) were obtained into the chamber; 2) for long flames, predominantly diffusive flames, just weak amplitudes were detected, in the spite of the speaker exiting the premixed flow; 3) when the energy is released distributed through the combustion chamber, the long flame acts like a baffle. Copyright © 2006 by the American Institute of Aeronautics and Astronautics, Inc. All rights reserved.