Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The average rate constant for loss of (45)Ca from an unpoisoned squid axon was 1.8 x 10(-3) min(-1), corresponding to an efflux of 0.2 p-mole/cm(2) sec.2. The Ca efflux from unpoisoned axons was reduced if external calcium was replaced with magnesium, or external sodium with lithium, choline or dextrose. Replacing both sodium and calcium reduced the efflux to about 40%.3. Cyanide caused little immediate change in Ca efflux but after 1(1/2)-2(1/2) hr the efflux increased to 5-15 times its normal value. The effect was rapidly reversed when cyanide was removed.4. The large Ca efflux into cyanide was reduced by a factor of three when external calcium was replaced with magnesium and by a further factor of about six when external sodium was replaced with lithium.5. The Ca efflux from both poisoned and unpoisoned axons had a Q(10) of 2-3, was not affected by ouabain and was greatly reduced by injecting ethyleneglycol bis (aminoethylether)-N,N'-tetra-acetic acid (EGTA).6. After injecting (45)Ca along the axis, the efflux of calcium reached its maximum much more rapidly in a cyanide-treated axon than in an unpoisoned axon.7. Pre-treatment with cyanide greatly increased the rate at which calcium was lost from axoplasm extruded into flattened dialysis bags. A similar effect was observed when cyanide was applied after extrusion.8. Replacing external sodium glutamate with potassium glutamate greatly reduced the loss of (45)Ca from intact axons poisoned with cyanide but had little effect on the loss from extruded axoplasm.9. The rate constant for loss of the Ca EGTA complex was about 3 x 10(-5) min(-1) for intact axons and 2 x 10(-2) min(-1) for extruded axoplasm.10. A possible explanation of the cyanide effect is that, after poisoning, calcium ions are released from a store and can then exchange at a higher rate with external sodium or calcium.11. The experiments suggest that part of the calcium efflux may be coupled to sodium entry.12. Theoretical equations for ;diffusion and chemical reaction in a cylinder' are described in the Appendix.
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PMID:The effect of cyanide on the efflux of calcium from squid axons. 576 8

L-type Ca channels contain a cluster of four charged glutamate residues (EEEE locus), which seem essential for high Ca specificity. To understand how this highly charged structure might produce the currents and selectivity observed in this channel, a theory is needed that relates charge to current. We use an extended Poisson-Nernst-Planck (PNP2) theory to compute (mean) Coulombic interactions and thus to examine the role of the mean field electrostatic interactions in producing current and selectivity. The pore was modeled as a central cylinder with tapered atria; the cylinder (i.e., "pore proper") contained a uniform volume density of fixed charge equivalent to that of one to four carboxyl groups. The pore proper was assigned ion-specific, but spatially uniform, diffusion coefficients and excess chemical potentials. Thus electrostatic selection by valency was computed self-consistently, and selection by other features was also allowed. The five external parameters needed for a system of four ionic species (Na, Ca, Cl, and H) were determined analytically from published measurements of thre limiting conductances and two critical ion concentrations, while treating the pore as a macroscopic ion-exchange system in equilibrium with a uniform bath solution. The extended PNP equations were solved with these parameters, and the predictions were compared to currents measured in a variety of solutions over a range of transmembrane voltages. The extended PNP theory accurately predicted current-voltage relations, anomalous mole fraction effects in the observed current, saturation effects of varied Ca and Na concentrations, and block by protons. Pore geometry, dielectric permittivity, and the number of carboxyl groups had only weak effects. The successful prediction of Ca fluxes in this paper demonstrates that ad hoc electrostatic parameters, multiple discrete binding sites, and logistic assumptions of single-file movement are all unnecessary for the prediction of permeation in Ca channels over a wide range of conditions. Further work is needed, however, to understand the atomic origin of the fixed charge, excess chemical potentials, and diffusion coefficients of the channel. The Appendix uses PNP2 theory to predict ionic currents for published "barrier-and-well" energy profiles of this channel.
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PMID:Ion permeation and glutamate residues linked by Poisson-Nernst-Planck theory in L-type calcium channels. 972 31

Protein kinase C displays high apparent cooperativity in its activation by phosphatidylserine. This contribution uses a novel approach to address the physical basis for this apparent cooperativity. We examine the binding of protein kinase C betaII to large unilamellar vesicles as a function of increasing mole fraction phosphatidylserine and as a function of increasing total lipid concentrations. Binding data are subjected to an analysis, described in the Appendix, that allows calculation of the fractional saturation of phosphatidylserine binding sites with this ligand. This analysis reveals that (1) protein kinase C betaII binds approximately eight phosphatidylserine molecules and (2) the binding of each lipid is not cooperative. Rather, the apparent cooperativity observed in protein kinase C's interaction with multiple phosphatidylserine molecules arises from effects specific to the interaction of a multivalent macromolecule with multiple membrane-associated ligands. Nor does diacylglycerol, which has been previously shown to dramatically increase protein kinase C's affinity for phosphatidylserine-containing membranes, induce cooperativity. Thus, protein kinase C binds multiple phosphatidylserine molecules in the absence of interaction between potential binding sites. The method presented for determining the stoichiometry and cooperativity in the interaction of protein kinase C with phosphatidylserine is applicable to any multivalent molecule binding to monovalent ligands incorporated into lipid membranes.
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PMID:Mechanism of the apparent cooperativity in the interaction of protein kinase C with phosphatidylserine. 986 Aug 41