The voltage-dependent inhibition of single N-type Ca(2+) channels by noradrenaline (NA) and the delta-opioid agonist D-Pen(2)-D-Pen (5)-enkephalin (DPDPE) was investigated in cell-attached patches of human neuroblastoma IMR32 cells with 100 mM Ba(2+) and 5 microM nifedipine to block L-type channels. In 70% of patches, addition of 20 microM NA + 1 microM DPDPE delayed markedly the first channel openings, causing a four- to fivefold increase of the first latency at +20 mV. The two agonists or NA alone decreased also by 35% the open probability (P(o)), prolonged partially the mean closed time, and increased the number of null sweeps. In contrast, NA + DPDPE had little action on the single-channel conductance (19 versus 19.2 pS) and minor effects on the mean open time. Similarly to macroscopic Ba(2+) currents, the ensemble currents were fast activating at control but slowly activating and depressed with the two agonists. Inhibition of single N-type channels was effectively removed (facilitated) by short and large depolarizations. Facilitatory pre-pulses increased P(o) significantly and decreased fourfold the first latency. Ensemble currents were small and slowly activating before pre-pulses and became threefold larger and fast decaying after facilitation. Our data suggest that slowdown of Ca(2+) channel activation by transmitters is mostly due to delayed transitions from a modified to a normal (facilitated) gating mode. This single-channel gating modulation could be well simulated by a Monte Carlo method using previously proposed kinetic models predicting marked prolongation of first channel openings.

High-voltage-activated (HVA) Ba2+ currents of rat insulinoma (RINm5F) and human pancreatic beta-cells were tested for their sensitivity to dihydropyridines (DHPs), omega-conotoxin (omega-CgTx) and noradrenaline. In RINm5F cells, block of HVA currents by nimodipine, nitrendipine and nifedipine was voltage- and dose-dependent (apparent KD < 37 nM) and largely incomplete even at saturating doses of DHPs (mean 53%, at 10 microM and 0 mV). Analysis of slow tail currents in Bay K 8644-treated cells indicated the existence of Bay K 8644-insensitive channels that turned on at slightly more positive voltages and deactivated more quickly than Bay K 8644-modified channels. DHP Ca2+ agonists and antagonists in human beta-cells had similar features to RINm5F cells except that DHP block was more pronounced (76%, at 10 microM and 0 mV) and Bay K 8644 action was more effective, suggesting a higher density of L-type Ca2+ channels in these cells. In RINm5F cells, but not in human beta-cells, DHP-resistant currents were sensitive to omega-CgTx. The toxin depressed 10-20% of the DHP-resistant currents sparing a "residual" current (25-35%) with similar voltage-dependent characteristics and Ca2+/Ba2+ permeability. Noradrenaline (10 microM) exhibited different actions on the various HVA current components: (1) it prolonged the activation kinetics of omega-CgTx-sensitive currents, (2) it depressed by about 20% the size of DHP-sensitive currents, and (3) it had little or no effects on the residual DHP- and omega-CgTx-resistant current although intracellularly applied guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) prolonged its activation time course.(ABSTRACT TRUNCATED AT 250 WORDS)

The seismicity of Italy between April 16, 2005 and December 31, 2010 is investigated by means of the visibility graph method. The degree distribution of the magnitude point process is power-law-shaped. The method does not seem to detect time-clustering structures in the magnitude point process. The degree distribution does not change significantly with the increase of the magnitude threshold from 1.9 to 3.5. The exponent of the degree distribution shows a certain stability vs. the threshold magnitude, ranging between 3.00 and 3.25, with mean value 3.11 ± 0.06.

The time structure of more than 10 years of hourly wind data measured in one site in northern Italy from April 1996 to December 2007 is analysed. The data are recorded by the Sodar Rass system, which measures the speed and the direction of the wind at several heights above the ground level. To investigate the wind speed time series at seven heights above the ground level we used two different approaches: i) the Multifractal Detrended Fluctuation Analysis (MF-DFA), which permits the detection of multifractality in nonstationary series, and ii) the Fisher-Shannon (FS) information plane, which allows to discriminate dynamical features in complex time series. Our results point out to the existence of multifractal time fluctuations in wind speed and to a dependence of the results on the height of the wind sensor. Even in the FS information plane a height-dependent pattern is revealed, indicating a good agreement with the multifractality. The obtained results could contribute to a better understanding of the complex dynamics of wind phenomenon.

[1] The detrended fluctuation analysis (DFA) is a powerful method for capturing scaling behavior in nonstationary time series. Using an appropriate instability index, it is possible to identify and quantify deviations from uniform power-law scaling, which suggest the presence of changing dynamics in the system under study. In this context, the scaling behavior of the 1981-2007 seismicity in Umbria-Marche (central Italy), which is one of the most seismically active areas in Italy, was investigated. Significant deviations from uniform power-law scaling in the seismic temporal fluctuations were revealed mostly linked with the occurrence of rather large earthquakes or seismic clusters. Citation: Telesca, L., and M. Lovallo (2009), Non-uniform scaling features in central Italy seismicity: A non-linear approach in investigating seismic patterns and detection of possible earthquake precursors, Geophys. Res. Lett., 36, L01308,

No abstract

High-threshold (HVA) Ca2+ channels of human neuroblastoma IMR32 cells were effectively inhibited by noradrenaline. At potentials between -20 mV and +10 mV, micromolar concentrations of noradrenaline induced a 50%-70% depression of HVA Ba2+ currents and a prolongation of their activation kinetics. Both effects were relieved at more positive voltages or by applying strong conditioning pre-pulses (facilitation). Facilitation restored the rapid activation of HVA channels and recruited about 80% of the noradrenaline-inhibited channels at rest. Re-inhibition of Ca2+ channels after facilitation was slow (tau r 36-45 ms) and voltage-independent between -30 mV and -90 mV. The inhibitory action of noradrenaline was dose-dependent (IC50 = 84 nM), mediated by alpha 2-adrenergic receptors and selective for omega-conotoxin-sensitive Ca2+ channels, which represent the majority of HVA channels expressed by IMR32 cells. The action of noradrenaline was mimicked by intracellular applications of GTP[gamma S] and prevented by GDP[beta S] or by pre-incubation with pertussis toxin. The time course of noradrenaline inhibition measured during fast application (onset) and wash-out (offset) of the drug were independent of saturating agonist concentrations (10-50 microM) and developed with mean time constants of 0.56 s (tau on) and 3.6 s (tau off) respectively. The data could be simulated by a kinetic model in which a G protein is assumed to modify directly the voltage-dependent gating of Ca2+ channels. Noradrenaline-modified channels are mostly inhibited at rest and can be recruited in a steep voltage-dependent manner with increasing voltages.

No abstract