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1.
Copper and zinc as modulators of neuronal excitability in a physiologically significant concentration range 总被引:1,自引:0,他引:1
Evidence from several areas of neuroscience has led to the notion that copper and zinc could be modulators of neuronal excitability. In order to contribute to test this idea, we characterized the changes induced by these divalent metal ions on the extracellularly recorded action potential firing rates of undissociated olfactory epithelium neurons. Our main finding is that at low concentrations, 1-100 nM for Cu(2+) and 1-50 microM for Zn(2+), they induced a concentration dependent increase in the neuronal firing rate. In contrast, at higher concentrations, 1-5 microM for Cu(2+) and 100-500 microM for Zn(2+), they decreased the firing rate. Based on these and previous results of our laboratory we propose that the biphasic effect of Cu(2+) and Zn(2+) exposure on neuronal firing may be explained by the interaction of these ions with high and low affinity sites in sodium channels whose occupancy leads to activation or inhibition of the sodium current, which is consistent with the proposed modulatory role of these metal ions on neuronal excitability. 相似文献
2.
K Krnjevi? Y Lamour J F MacDonald A Nistri E Puil R Werman 《Canadian journal of physiology and pharmacology》1979,57(9):957-972
Itracellular injections of Mg into cat spinal motoneurones have a depolarizing action, associated with a fall in input conductance, and depression of the postspike hyperpolarizing after-potential (a.h.p.) as well as its underlying conductance increase. There is also an increase in excitability, sometimes leading to outright discharge, and a change in the current-firing relation: the normal primary range is largely abolished and the firing appears to have the characteristics of the normal secondary range. Intracellular effects of Mg are thus mainly opposite to those of Ca, possibly owing to competition at sites where Ca activates K channels. Intracellular injections of Mn also tend to depress the a.h.p. but have relatively little effect on resting potential and conductance, or action potentials. Co also depresses the a.h.p. but has a more pronounced depolarizing action, and produces particularly strong depression of action potentials. By contrast intracellular Sr tends to raise the membrane conductance and has a mild hyperpolarizing effect. During the injection of Sr, a.h.p's are depressed but this is followed by a rebound of increased a.h.p. amplitude and conductance. Unlike the other divalent cations tested, Sr strongly depressed excitatory postsynaptic potentials. In most respects Sr appears to behave like Ca. 相似文献
3.
E A Permiakov L A Kalinichenko L A Morozova Iu V Derezhkov J Bagelova 《Molekuliarnaia biologiia》1988,22(4):984-991
Interactions of the calcium binding proteins, parvalbumin from cod muscles, alpha-lactalbumin from cow milk and calmodulin from bovine brain, with Cu2+ and Zn2+ ions have been studied by intrinsic fluorescence and microcalorimetry methods. It was revealed that parvalbumin binds one Cu2+ ion per molecule with association constant from 10(5) to 10(6) M-1. Zn2+ ions seem to compete for the same site which does not coincide with the two Ca2+ and Mg2+ binding sites. alpha-Lactalbumin contains from 2 to 4 Cu2+ and Zn2+ binding sites, the number and affinities of which depend on Ca2+ concentration. Calmodulin has similar Cu2+ and Zn2+ binding sites. The binding of Cu2+ and Zn2+ ions to parvalbumin and alpha-lactalbumin changes the shape and position of their thermal denaturation transitions. The results obtained together with the literature data show that the ability to interact with Cu2+ and Zn2+ ions is a property inherent to many calcium-binding proteins, which may play a physiological role for some of them. 相似文献
4.
Divalent cations and electrical properties of cortical cells 总被引:1,自引:0,他引:1
5.
M. Pusch 《European biophysics journal : EBJ》1990,18(6):327-333
1. Several cloned sodium channels were expressed in oocytes and compared with respect to their sensitivity to internal Mg2+ concerning the open-channel block and to external Ca2+ concerning open-channel block and shifts in steady-state activation. 2. A quantitative comparison between wild-type II channels and a mutant with a positive charge in the S4 segment of repeat I neutralized (K226Q) revealed no significant differences in the Mg2+ block. 3. The blocking effect of extracellular Ca2+ ions on single-channel inward currents was studied for type II, mutant K226Q and type III. A quantitative comparison showed that all three channel types differ significantly in their Ca+ sensitivity. 4. The influence of extracellular Ca2+ on the voltage dependence of steady-state activation of macroscopic currents was compared for type II and K226Q channels. Extracellular Ca+ increases the voltage of half-maximal activation, V1/2, more for K226Q than for wild-type II channels; a plot of V
1/2 against [Ca]
o
, is twice as steep for the mutant K226Q as for the wild-type on a logarithmic concentration scale. 5. The differential effects of extracellular Ca+ and intracellular Mg2+ on wild-type II and K226Q channels are discussed in terms of structural models of the Na+ channel protein.Abbreviations [Na]
i
intracellular Na+ concentration
- [Mg]
intracellular Mg2+ concentration
- [Ca]
o
extracellular Ca2+ concentration 相似文献
6.
Aaron James Camp Rajiv Wijesinghe 《The international journal of biochemistry & cell biology》2009,41(11):2118-2121
Calretinin is a member of the calcium-binding protein EF-hand family first identified in the retina. As with the other 200-plus calcium-binding proteins, calretinin serves a range of cellular functions including intracellular calcium buffering, messenger targeting, and is involved in processes such as cell cycle arrest, and apoptosis. Calcium-binding proteins including calretinin are expressed differentially in neuronal subpopulations throughout the vertebrate and invertebrate nervous system and their expression has been used to selectively target specific cell types and isolate neuronal networks. More recent experiments have revealed that calretinin plays a crucial role in the modulation of intrinsic neuronal excitability and the induction of long-term potentiation (LTP). Furthermore, selective knockout of calretinin in mice produces disturbances of motor coordination and suggests a putative role for calretinin in the maintenance of calcium dynamics underlying motor adaptation. 相似文献
7.
The Mg(2+) content of membranes of several Mycoplasma and Acholeplasma species varied between 0.88 and 1.98 mug of Mg(2+) per mg of protein, depending on the species and on growth conditions. Ca(2+) could be detected only when it was added to the growth medium. The Mg(2+) content of isolated A. laidlawii membranes could be increased almost threefold by dialysis against 20 mm Mg(2+), whereas aggregated A. laidlawii membranes contained about six to eight times more Mg(2+) per mg of protein than the native membranes. This was taken to indicate that the molecular organization of the lipid and protein in the reaggregated membranes differs from that of the native membranes. Between 60 and 83% of the Mg(2+) in native and reaggregated A. laidlawii membranes was associated with the lipid fraction extracted with chloroform-methanol. The removal of over 80% of membrane protein by Pronase digestion did not release any significant amount of Mg(2+). Hence, most of the divalent cation appears to be bound to membrane lipids, most probably to phospholipids. Ethylenediaminetetraacetic acid released the bulk of Mg(2+) bound to the native and reaggregated A. laidlawii membranes, except for about 0.5 mug of Mg(2+) per mg of protein which was too tightly bound. Hence, a small but fairly constant amount of Mg(2+) is unavailable for chelation. 相似文献
8.
Blindauer CA 《Journal of inorganic biochemistry》2008,102(3):507-521
For many years, paradigms regarding metallothioneins comprised the exclusive metal coordination by thiolates from cysteine residues and the absence of aromatic residues. As more sequence and in vitro data on metallothioneins, in particular from non-vertebrate organisms, has become available, both the occurrence of and metal coordination by histidine residues in metallothioneins is emerging as a more frequent feature than expected. We discuss the general implications of histidines versus cysteines in zinc binding sites, and review some recent results from literature and our own lab. We conclude that histidines can stabilise metallothionein clusters by reducing the overall charge, offering the ability to help with structural organisation by supplying H-bond donor and acceptor properties, reducing the likelihood for disulfide bond formation, whilst maintaining a high affinity towards metal ions, in particular the borderline zinc ion. 相似文献
9.
Investigation of the development of excitability has revealed that cells are often specialized at early stages to generate Ca(2+) transients. Studies of excitability have converged on the central role of Ca(2+) and K(+) channels in the plasmalemma that regulate Ca(2+) influx and have identified critical functions for receptor-activated channels in the endoplasmic reticulum that allow efflux of Ca(2+) from intracellular stores. The parallels between excitability in these two locations motivate future work, because comparison of their properties identifies shared attributes. 相似文献
10.
11.
Leonhard-Marek S 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2002,172(7):635-641
The rumen epithelium of sheep and goats showed an increase in short circuit current ( Isc) and transepithelial conductance (gt) upon mucosal removal of divalent cations. A divalent-sensitive Isc and gt were present in Na+, K+ or Rb+ buffer, but nearly abolished in mucosal NMDG+ (N-methyl-D-glucamine) buffer. High K buffer, addition of BaCl2 or of ouabain on the serosal side also reduced or abolished the divalent-sensitive Isc. Mucosal Ca2+ was more potent in blocking Isc, but had the same potency as Mg2+ in blocking gt. A prolonged mucosal deprivation of Mg2+ ions increased gt, potential difference and basal as well as the Ca2+-sensitive Isc. Mucosal addition of Mg2+ had a smaller effect on gt after serosal preincubation with Ba. The data suggest that rumen epithelial cells exhibit an apical non-selective cation conductance, which permits the passage of monovalents in the mucosal absence of divalents. The development of a divalent-sensitive Isc in Na buffer requires Na+/K+ pumps and K+ recycling through Ba2+-sensitive K+ conductances on the basolateral side. This Isc is blocked by extracellular Ca2+ and both extracellular and intracellular Mg2+ ions. A prolonged deprivation of mucosal Mg2+ alone seems to affect intracellular Mg2+ in this Mg2+-absorbing tissue. 相似文献
12.
Transmitter release from frog motor terminals was studied in the presence of very low concentrations of tetrodotoxin (TTX, 4.10(-10)--6.10(-9) g/ml). TTX reversibly reduced the amplitude of the end-plate potential (epp), while leaving the amplitude distribution to follow Poisson's law. The effects of a number of divalent cations were studied in the presence of TTX. It was found that after the addition of TTX there was an increase in the constant of dissociation of calcium and strontium from a hypothetical membrane "release site," while the dissociation constants of magnesium and manganese remained unaltered. It is concluded that the release site is probably intracellular and that a reduced presynaptic spike amplitude, as well as magnesium and manganese ions, decrease the access of calcium and strontium to the site. 相似文献
14.
Valtorta F Pozzi D Benfenati F Fornasiero EF 《Seminars in cell & developmental biology》2011,22(4):378-386
Neurons are examples of specialized cells that evolved the extraordinary ability to transmit electrochemical information in complex networks of interconnected cells. During their development, neurons undergo precisely regulated processes that define their lineage, positioning, morphogenesis and pattern of activity. The events leading to the establishment of functional neuronal networks follow a number of key steps, including asymmetric cell division from neuronal precursors, migration, establishment of polarity, neurite outgrowth and synaptogenesis. Synapsins are a family of abundant neuronal phosphoproteins that have been extensively studied for their role in the regulation of neurotransmission in presynaptic terminals. Beside their implication in the homeostasis of adult cells, synapsins influence the development of young neurons, interacting with cytoskeletal and vesicular components and regulating their dynamics. Although the exact molecular mechanisms determining synapsin function in neuronal development are still largely unknown, in this review we summarize the most important literature on the subject, providing a conceptual framework for the progress of present and future research. 相似文献
15.
Melkani GC Sielaff RL Zardeneta G Mendoza JA 《Biochemical and biophysical research communications》2008,368(3):625-630
The divalent cations Mg2+, Mn2+, Zn2+, Ca2+, and Ni2+ were found to protect against proteolysis a form of GroEL (ox-GroEL) prepared by exposing GroEL for 16 h to 6 mM hydrogen peroxide (H2O2). K+ and other monovalent cations did not have any effect. Divalent cations also induced a conformational change of ox-GroEL that led to the decrease of its large exposed hydrophobic surfaces (exposed with H2O2). Ox-GroEL incubated with a divalent cation behaved like N-GroEL in that it could transiently interact with H2O2-inactivated rhodanese (ox-rhodanese), whereas ox-GroEL alone could strongly interact with ox-rhodanese. Although, ox-GroEL incubated with a divalent cation could not recover the ATPase activity (66%) lost with H2O2, it could facilitate the reactivation of ox-rhodanese (>86% of active rhodanese recovered), without requiring ATP or the co-chaperonin, GroES. This is the first report to demonstrate a role for the divalent cations on the structure and function of ox-GroEL. 相似文献
16.
In the presented review given literature and results of own studies of dynamics of electrical characteristics of neurons, which change are included in processes both an elaboration of learning, and retention of the long-term memory. Literary datas and our results allow to conclusion, that long-term retention of behavioural reactions during learning is accompanied not only by changing efficiency of synaptic transmission, as well as increasing of excitability of command neurons of the defensive reflex. This means, that in the process of learning are involved long-term changes of the characteristics a membrane of certain elements of neuronal network, dependent from the metabolism of the cells. see text). Thou phenomena possible mark as cellular (electrophysiological) correlates of long-term plastic modifications of the behaviour. The analyses of having results demonstrates an important role of membrane characteristics of neurons (their excitability) and parameters an synaptic transmission not only in initial stage of learning, as well as in long-term modifications of the behaviour (long-term memory). 相似文献
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18.
The predictions of counterion condensation theory for divalent ions were tested by comparison with the results of Monte Carlo calculations on an all-atom model of DNA. Monovalent-divalent competition at the polyelectrolyte surface was investigated by varying the partial molar volume of divalent ions. To assess the viability of using Poisson-Boltzmann (PB) calculations for determining divalent ion concentrations at DNA surfaces, Monte Carlo (MC) calculations were compared with PB calculations using different models of the dielectric continuum. It was determined that, while standard PB calculations of divalent ion surface densities are about 25-30% below those predicted by MC techniques, and somewhat larger than errors previously determined for monovalent ions, errors due to the use of the mean-field approximation of PB theory are smaller than those arising from common assumptions regarding the dielectric continuum. 相似文献
19.
20.
Nucleotides and divalent cations as effectors and modulators of exocytosis in permeabilized rat mast cells. 总被引:4,自引:0,他引:4
T H Lillie B D Gomperts 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1992,336(1276):25-34
The idea that the universal trigger to exocytosis (the terminal step in the secretory process) is an elevation of the cytosol concentration of Ca2+, and that it is dependent on ATP, is no longer tenable. Working with streptolysin-O-permeabilized mast cells (and other myeloid cells) we have shown that non-hydrolysable analogues of GTP can stimulate exocytosis after depletion of Ca2+ (i.e. at concentrations below 10(-9) M) and ATP. Such Ca2+- and ATP-independent exocytosis is strongly dependent on the presence of Mg2+, and the requirement for Mg2+ declines as the concentration of Ca2+ is brought up to 10(-7) M. We argue that Ca2+ serves to regulate the binding of guanine nucleotides to GE, a GTP-binding protein that regulates exocytosis through its interaction with CE, a calcium-binding protein which serves as an intracellular pseudo-receptor. The onset of exocytosis, following provision of Ca2+ and guanine nucleotides to the permeabilized cells, is preceded by delays which are sensitive to the order of provision of the two effectors (i.e. Ca2+ and guanine nucleotides), the presence or absence of Mg2+, and the identity of the activating guanine nucleotide. In view of the similarity of these features with the activation kinetics of adenylyl cyclase, we argue that GE behaves as a member of the heterotrimeric class of signal transducing G-proteins such as GS. 相似文献