1,096 research outputs found
An enzymatic mechanism for calcium current inactivation in dialysed Helix neurones
No full text'Wash-out' and inactivation of the Ca current were examined in dialysed, voltage-clamped neurones of Helix aspersa under conditions that isolate the Ca current virtually free of other currents. EGTA or other internal Ca2+ chelators were routinely omitted from the dialysate. The time-dependent loss, or wash-out, of Ca current was slowed by addition to the dialysing solution of agents, such as dibutyryl adenosine 3'-5'-cyclic monophosphate (dibutyryl cyclic AMP), Mg adenosine 5'-triphosphate (ATP) and the catalytic subunit of cyclic-AMP-dependent protein kinase, that promote protein phosphorylation and by EGTA. However, neither the phosphorylation-promoting agents nor internal EGTA prevented wash-out entirely, nor did they significantly restore previously 'washed-out' current. With phosphorylating agents in the dialysing solution, the irreversible development of wash-out was greatly reduced by introduction of leupeptin, an inhibitor of protease activity. Thus, the irreversible component of wash-out appears to result from a Ca-dependent proteolytic process. In the presence of leupeptin alone, Ca current amplitude continued to decline: however, the current could be largely or fully restored with addition of catalytic subunit, dibutyryl cyclic AMP, and Mg ATP to the dialysing solution. Thus, inhibition of proteolysis revealed a reversible component of wash-out that appears to result from dephosphorylation. During perfusion with leupeptin, Mg ATP, dibutyryl cyclic AMP and catalytic subunit the Ca current remained stable for up to several hours without addition of internal Ca2+ buffer. The rate of inactivation of the current that occurs during a depolarizing step showed only a very gradual decline during this time. Under these conditions, perfusion with calcineurin, a Ca-calmodulin-dependent phosphatase, caused a significant increase in the rate of Ca current inactivation. This inactivation was virtually eliminated by introduction of EGTA or by replacement of external Ca2+ with Ba2+, which is consistent with the ion dependency for calmodulin-dependent activation of calcineurin. When ATP in the dialysate was replaced with ATP-gamma-S (adenosine 5'-O-(thiotriphosphate], an analogue that donates a thiophosphate group resistant to hydrolysis, the rate of inactivation slowed. Since Ca-dependent inactivation during step depolarizations is enhanced by conditions that promote dephosphorylation, and Ca current wash-out is slowed by conditions that promote phosphorylation, inactivation and reversible wash-out appear to be related
Behavioral simulation and synthesis of biological neuron systems using synthesizable VHDL
No full textNeurons are complex biological entities which form the basis of nervous systems. Insight can be gained into neuron behavior through the use of computer models and as a result many such models have been developed. However, there exists a trade-off between biological accuracy and simulation time with the most realistic results requiring extensive computation. To address this issue, a novel approach is described in this paper that allows complex models of real biological systems to be simulated at a speed greater than real time and with excellent accuracy. The approach is based on a specially developed neuron model VHDL library which allows complex neuron systems to be implemented on field programmable gate array (FPGA) hardware. The locomotion system of the nematode Caenorhabditis elegans is used as a case study and the measured results show that the real time FPGA based implementation performs 288 times faster than traditional ModelSim simulations for the same accuracy
Ca current inactivation is slowed in dialyzed snail neurons by the substitution of atp-gamma-s for internal atp
No full textModulation of synaptic responses in CAl pyramidal neurones of the rat hippocampus by activation of presynaptic GABA(B) receptors
No full textSummation of membrane current conductance responses as evidence for independent ionophore populations
No full text1. The ramped voltage clamp technique was utilized to measure the maximum conductance changes in response to the application of pairs of agonists.2. Two types of cells were investigated. (a) depolarized by ACh and 5-HT. (b) hyperpolarized by ACh and glutamate.3. Membrane conductance was increased to the same ionic species by each pair of agonists in the cells investigated.4. Membrane conductance increases to simultaneous application of two agonists were equal to the arithmetic sum of membrane conductance changes to the sequential addition of the same doses of agonists, even when responses were maximal.5. There was no competition between the pairs of agonists for a common ionophore population
The acetylcholine induced membrane current fluctuations are characteristic of the receptor-ionophore population involved
No full text1. Clamp current recordings from voltage clamped Helix aspersa neurones show increased membrane current fluctuations during the three types of acetylcholine (ACh) response studied.2. The variance of the ACh induced membrane current fluctuations was proportional to the mean clamp current and was steady during data acquisition. The mean channel current (iel) could be calculated from these values.3. The power spectrum (PSD) of the ACh induced membrane current fluctuations for both the pure ionic responses [ACh D increased gNa+ and ACh H incrased gCl?] could be fitted by single Lorentzian curves.4. The corner frequency (fc) of the PSD differed between the D and H responses, being 15.9 Hz and 48 Hz respectively, corresponding to mean channel open times (Tm) of 10 msec for the Na+ channel and 3.3 msec for the Cl? channel.5. The PSD of the ACh induced membrane current fluctuations of the mixed ionic response [D(f Cl) increased gNa+ adn gCl?] could not be fitted by a single Lorentzian curve, but could be fitted by the arithmetic sum of two Lorentzian curves, with corner frequencies of 12.5 Hz and 50 Hz. These values for fc correspond to Tms of 15.9 msec and 3.2 msec.6. It is suggested that the double Lorentzian of the D(f Cl) response is due to activation of a heterogeneous receptor-ionophore population consisting of two classes which correspond to the D receptor/Na+ ionophore and H receptor/Cl? ionophore present on the other cell types studied
Calcium domains associated with individual channels can account for anomalous voltage relations of CA-dependent responses
No full textComputer-assisted modeling of calcium influx through voltage-activated membrane channels predicted that buffer-limited elevation of cytoplasmic free calcium ion concentration occurs within microscopic hemispherical "domains" centered upon the active Ca channels. With increasing depolarization, the number of activated channels, and hence the number of Ca domains, should increase; the single-channel current should, however, decrease, thereby decreasing Ca2+ accumulation in each domain relative to the macroscopic current. Such voltage dependence of the microscopic distribution of Ca2+ may influence relations between total Ca2+ entry and Ca-dependent processes. Ca-mediated inactivation of Ca channels in Aplysia neurons exhibits behavior consistent with the calcium domain hypothesis
Windfall management for poverty reduction : improving public finance Management-the case of Chad
No full textThis paper aims at providing a guide to ensure efficiency in the management of Chad's windfall to support the development process and poverty reduction. The analysis is based on the lessons and experience of countries that have successfully used natural-resource-generated windfalls to launch their development process while avoiding the natural resource curse. The paper also discusses the petroleum management arrangements in place in Chad for poverty reduction. The author argues that the successful management of Chad's windfall for poverty reduction will depend on the effectiveness of oil revenue management arrangements in place in Chad and the government's willingness to improve public finance management (PFM).Public Sector Expenditure Analysis&Management,Debt Markets,,Public Sector Economics&Finance,Banks&Banking Reform
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