Biophysical re-equilibration of Ca2+ fluxes as a simple biologically plausible explanation for complex intracellular Ca2+ release patterns

Physiological regulation of Ca(2+) release from the endoplasmic reticulum (ER) is critical for cell function. Recent direct measurements of free [Ca(2+)] inside the ER ([Ca(2+)](ER)) revealed that [Ca(2+)](ER) itself is a key regulator of ER Ca(2+) handling. However, the role of this new regulatory process in generating various patterns of Ca(2+) release remains to be elucidated in detail. Here, we incorporate the recently quantified experimental correlations between [Ca(2+)](ER) and Ca(2+) movements across the ER membrane into a mathematical model ER Ca(2+) handling. The model reproduces basic experimental dynamics of [Ca(2+)](ER). Although this was not goal in model design, the model also exhibits mechanistically unclear experimental phenomena such as "quantal" Ca(2+) release, and "store charging" by increasing resting cytosolic [Ca(2+)]. While more complex explanations cannot be ruled out, on the basis of our data we propose that "quantal release" and "store charging" could be simple re-equilibration phenomena, predicted by the recently quantified biophysical dynamics of Ca(2+) movements across the ER membrane.     

Experimental study of the dynamics of neutron emission from the GOL-3 multimirror trap

In experiments on the plasma heating and confinement in the GOL-3 multimirror trap, a deuterium plasma with a density of ～10¹⁵ cm^?3 and an ion temperature of 1–2 keV is confined for more than 1 ms. The plasma is heated by a relativistic electron beam. The ion temperature, which was measured by independent methods, reached 1.5–2 keV after the beginning of the beam injection. Since such a fast ion heating cannot be explained by the classical energy transfer from electrons to ions through binary collisions, a theoretical model of collective energy transfer was proposed. In order to verify this model, a new diagnostics was designed to study the dynamics of neutron emission from an individual mirror cell of the multimirror trap during electron beam injection. Intense neutron bursts predicted by this model were detected experimentally. Periodic neutron flux modulation caused by the macroscopic plasma flow along the solenoid was observed. The revealed mechanism of fast ion heating can be used to achieve fusion temperatures in the multimirror trap.     

Diagnostic system for studying generation of subterahertz radiation during beam-plasma interaction in the GOL-3 facility

The design principles and construction of the subterahertz radiometric spectral systems developed for the GOL-3 facility are described. The spectral systems are designed according to the quasi-optical scheme and use multilayer filters based on frequency-selective surfaces. The design and manufacturing technology of such elements are discussed. The results of measuring subterahertz radiation of plasma at the frequency close to the double plasma frequency are presented.     

Multichannel Thomson scattering diagnostics for the GOL-3 facility

A multichannel Thomson scattering diagnostics for measuring the plasma parameters in the GOL-3 facility was designed and created at the Budker Institute of Nuclear Physics of the Siberian Division of the Russian Academy of Sciences. The diagnostics operates at the fundamental harmonic of a neodymium laser (1.06 μm) and allows one to perform measurements over a wide range of electron temperatures and densities with high spatial and time resolutions. A special multipulse oscillator is developed that makes it possible to perform up to 20 measurements of the plasma temperature and density over a period of 300 μs during one shot. The laser used to generate probing radiation, the recording system, and the calibration procedure are described. Results from measurements of the temporal evolution of the plasma density in the GOL-3 in different stages of the discharge are presented to illustrate the system operation. Original Russian Text ? S.V. Polosatkin, A.V. Burdakov, M.V. Ivantsivskiĭ, V.S. Koĭdan, V.K. Ovchar, A.F. Rovenskikh, V.V. Semionov, M.G. Fedotov, 2006, published in Fizika Plazmy, 2006, Vol. 32, No. 2, pp. 128–133.     

Measurements of the electron energy spectrum by using small-angle Thomson scattering

A novel diagnostic method is developed for studying the high-energy plasma electron component in the GOL-3 facility by using small-angle Thomson scattering. The method is based on the enhancement of the spectral density of scattered radiation as compared to the conventional large-angle scattering technique.     

Generation of specific Ca(2+) signals from Ca(2+) stores and endocytosis by differential coupling to messengers

It remains unclear how different intracellular stores could interact and be recruited by Ca(2+)-releasing messengers to generate agonist-specific Ca(2+) signatures. In addition, refilling of acidic stores such as lysosomes and secretory granules occurs through endocytosis, but this has never been investigated with regard to specific Ca(2+) signatures. In pancreatic acinar cells, acetylcholine (ACh), cholecystokinin (CCK), and the messengers cyclic ADP-ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and inositol 1,4,5-trisphosphate (IP(3)) evoke repetitive local Ca(2+) spikes in the apical pole. Our work reveals that local Ca(2+) spikes evoked by different agonists all require interaction of acid Ca(2+) stores and the endoplasmic reticulum (ER), but in different proportions. CCK and ACh recruit Ca(2+) from lysosomes and from zymogen granules through different mechanisms; CCK uses NAADP and cADPR, respectively, and ACh uses Ca(2+) and IP(3), respectively. Here, we provide pharmacological evidence demonstrating that endocytosis is crucial for the generation of repetitive local Ca(2+) spikes evoked by the agonists and by NAADP and IP(3). We find that cADPR-evoked repetitive local Ca(2+) spikes are particularly dependent on the ER. We propose that multiple Ca(2+)-releasing messengers determine specific agonist-elicited Ca(2+) signatures by controlling the balance among different acidic Ca(2+) stores, endocytosis, and the ER.     

Creation of a long magnetized plasma column in a metal chamber

A method for creation of a long magnetized column of dense hydrogen plasma in a metal chamber by means of a high-current linear discharge is considered. It is the main method for the formation of preliminary plasma in the GOL-3 multimirror trap, in which a plasma column with a length of up to 12 m and diameter of 8 cm, suitable for conducting experiments on the injection of a relativistic electron beam, was obtained. Conditions for stable discharge operation in the density range of 3 × 10¹⁹–10²² m^?3 are determined, including a discharge with a uniform longitudinal plasma density profile and incomplete initial ionization of hydrogen. It is demonstrated that the system is capable of operating in a magnetic field with a variable configuration and strength of up to 6 T in the solenoidal section and up to 12 T in the end mirrors. It is shown that an important role in the development of a discharge is played by fast electrons with energies corresponding to the initial applied voltage (about 25 kV), which provide primary gas ionization. The properties of low-temperature plasma in such a discharge are discussed.     

Differential rotation of plasma in the GOL-3 multiple-mirror trap during injection of a relativistic electron beam

Results of spectral and magnetic diagnostics of plasma differential rotation in the GOL-3 multiplemirror trap are presented. It is shown that the maximum frequency of plasma rotation about the longitudinal axis reaches 0.5 MHz during the injection of a relativistic electron beam into the plasma. The data of two diagnostics agree if there is a region with a higher rotation frequency near the boundary of the electron beam. Plasma differential rotation can be an additional factor stabilizing interchange modes in the GOL-3 facility.     

Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose

Glucose-inhibited neurons orchestrate behavior and metabolism according to body energy levels, but how glucose inhibits these cells is unknown. We studied glucose inhibition of orexin/hypocretin neurons, which promote wakefulness (their loss causes narcolepsy) and also regulate metabolism and reward. Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K(+) (K(2P)) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca(2+), or glucose itself. These results reveal an unexpected energy-sensing pathway in neurons that regulate states of consciousness and energy balance.     

Metabolic state signalling through central hypocretin/orexin neurons

Hypothalamic neurons that produce the peptide transmitters hypocretins/orexins have attracted much recent attention. They provide direct and predominantly excitatory inputs to all major brain areas except the cerebellum, with the net effect of stimulating wakefulness and arousal. These inputs are essential for generating sustained wakefulness in mammals, and defects in hypocretin signalling result in narcolepsy. In addition, new roles for hypocretins/orexins are emerging in reward-seeking, learning, and memory. Recent studies also indicate that hypocretin/orexin neurons can alter their intrinsic electrical activity according to ambient fluctuations in the levels of nutrients and appetite-regulating hormones. These intriguing electrical responses are perhaps the strongest candidates to date for the elusive neural correlates of after-meal sleepiness and hunger-induced wakefulness. Hypocretin/orexin neurons may thus directly translate rises and falls in body energy levels into different states of consciousness.