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Biomedical subjects

E A Liberman

Publications and source records attributed to E A Liberman.

At least 19 recordsLinked to original sources

Mechanical influence and cAMP injection evoke the same reaction of neuron ionic channels.

Intracellular cAMP injection and negative pressure in the patch-electrode increase the interburst closed time of the same potassium ionic channels in the snail neuron membrane. Sodium channels which were registered as change of background noise are activated both by cAMP injection and by negative pressure. These results are considered in connection with data about the unusual biochemistry of the neuron reaction to cAMP.

Animals

Quantum molecular computer model of the neuron and a pathway to the union of the sciences.

Cyclic nucleotide injection in neurons shows that cAMP controls a new type of membrane permeability. The neuron response to cAMP has a short delay, unusual bioenergetics and is blocked by drugs binding with the regulatory subunit of protein kinase. These data are interpreted in terms of the hypothesis that the controlling system of the living cell is a molecular (DNA, RNA, protein operators with complementary addresses), holographic (quick changeable lattice--cytoskeleton), quantum (each phonon examines whole lattice), hypersound (with wave length 100-10,000 A that does not destroy molecules) system with an inner point of view (molecular coding of questions and answers about quantum processing). Neither an electron, nor a macroscopic computer has an inner point of view.

Biology

Analog-digital molecular cell computer.

The living cell is controlled by a molecular stochastic computer of parallel-successive action. MCC may be equivalent to the universal computer. MCC operates with molecule-words (DNA, RNA, proteins) according to the programme recorded in DNA and RNA. Operations are produced by molecular devices (RNA- and DNA-polymerases, ligases, proteinases and so on). Molecular devices operating with molecule-words are recorded on molecules themselves, and they are read off by ribosomes. Therefore the programme of the reorganization of the programme itself may be recorded on the molecule-words. MCC operates with molecular words having definite addresses. The words and the operators collide by Brownian movement and combine if the molecular surface of address segment is complementary and properly oriented. It is possible to reproduce not only the programmes but also the operators of MCC. The molecular computer operates with word-molecules according to the programme, recorded in DNA, with the aim of predicting an outer situation in the next time-moment and selecting of a correct answer by synthesis of suitable proteins and other substances and also by macroscopic motion. Each step of directed calculation is needed of the consumption of minimally necessary portion of free energy and search is due to the Brownian movement without free energy loss. Cyclic nucleotides are intraneuron membrane potential controlling systems which can be described as molecular diffusional analog computers, well fitted to solve mathematical physics equations if there are high frequency generators and regulators of cyclic nucleotides sources and sinks. It is suggested that molecular proton channels in an electric field are such generators of 10(11)-10(12) Hz. Biophysics cannot use the ordinary laws of physics and must take into account the influence on the phenomena to be studied, not only of a measurement but also of a calculation process in the real device predicting the future.

Biophysical Phenomena

Reconstitution of Biological Molecular generators of electric current. Bacteriorhodopsin.

1. Photoinduced generation of electric current by bacteriorhodopsin, incorporated into the planar phospholipid membrane, has been directly measured with conventional electrometer techniques. 2. Two methods for bacteriorhodopsin incorporation have been developed: (a) formation of planar membrane from a mixture of decane solution of phospholipids and of the fraction of violet fragments of the Halobacterium halobium membrane (bacteriorhodopsin sheets), and (b) adhesion of bacteriorhodopsin-containing reconstituted spherical membranes (proteoliposomes) to the planar membrane in the presence of Ca2+ or some other cations. In both cases, illumination was found to induce electric current generation directed across the planar membrane, an effect which was measured by macroelectrodes immersed into electrolyte solutions on both sides of the membrane. 3. The maximal values of the transmembrane electric potential were of about 150 mV at a current of about 10(-11) A. The electromotive force measured by means of counterbalancing the photoeffect by an external battery, was found to reach the value of 300 mV. 4. The action spectrum of the photoeffect coincides with the bacteriorhodopsin absorption spectrum (maximum about 570 nm). 5. Both components of the electrochemical potential of H+ ions (electric potential and delta pH) across the planar membrane affect the bacteriorhodopsin photoelectric response in a fashion which could be expected if bacteriorhodopsin were a light-dependent electrogenic proton pump. 6. La3+ ions were shown to inhibit operation of those bacteriorhodopsin which pump out H+ ions from the La3+-containing compartment. 7. The photoeffect, mediated by proteoliposomes associated with thick planar membrane, is decreased by gramicidin A at concentrations which do not influence the planar membrane resistance in the light. On the contrary, a protonophorous uncoupler, trichlorocarbonylcyanidephenylhydrazone, decreases the photoeffect only if it is added at a concentration lowering the light resistance. The dark resistance is shown to be higher than the light one, and decreases to the light level by gramicidin. 8. A simple equivalent electric scheme consistent with the above results has been proposed.

Bacteriorhodopsins

[Cell molecular computer. IX. Coding principles in intracellular information processing].

Methods of coding the number and search for molecular program in a molecular computer are considered. The limited length of the nucleotide code is (see formula) where Pi -- probability of request of the given program, N -- total number of programs. Energetic expenditures for the synthesis of the code with the length l (in an ideal case without noise) E approximately 10 kT X l. Protein-nucleic recognition allows the work of the cell with almost the same expenditures on the account of Brown search in the presence of noise.

Cells

[Study of the mechanism of action of fasciolocides using bimolecular phospholipid membranes].

The effects of compounds (see article), where M = -S-, -SO-, -SO2- and of some of their derivatives (18 substances) on electroconductivity of bimolecular lipid membranes (BLM) of different composition in 30 mM tris-HCl (pH 7.5) is studied. The results obtained are compared with literature data concerning fasciolocide and toxic effect of these substances. Certain correlations are found between the action on BLM and biological effects of substances. The analysis of the results allowed a conclusion that the latter are concerned with a discoupling effect of substances on oxidative phosphorylation in mitochondria of helmets and their host. BLM may be applied for evaluating the value of fasciolocide and toxic effects of the substances protonophores.

Antiplatyhelmintic Agents

[Effect of ultraviolet light on sterol-containing membranes in nystatin solutions].

The nystatin induced conductivity of artificial phospholipid membranes containing ergosterol or 7-dehydrocholesterol drops sharply under the action of ultra-violet light as a result of the transformation of these provitamins into adequate D2 and D3 vitamins. The UV-light does not change the conductivity of the membranes containing cholestrol in nystatin solution. Nystatin slightly effects the membrane resistance in the presence of D2 and D3 vitamins.

Cholestanol

[Cell molecular computer. VII. Cell biophysics and realistic or information physics (1)].

Living organisms measure many parameters in order to have orientation in the outer medium. That is why biophysics cannot use the ordinary laws of physics and must take into account the influence on the phenomena to be studied not only of a measurement but also of a calculation process in the real physical and biophysical device predicting the future. Science taking into account the effects of the calculating process-realistical or informative (RI) physics-has different (laws) for different times, distances and numbers of measuring and predicting parameters. RI-physics deals with unreproducible events and considers only such time intervals and distances for which the prediction can be made on the basis of earlier measurements and calculations according to the laws with optimal difficulty. It is suggested that the living cell uses the laws which are close to these optimal (limiting) laws of RI-physics. Physics and quantum mechanics can be considered as a limiting case of RI-physics. In this case values of distances and times are large enough and the number of simultaneously measured independent parameters is such that the heat effect of the calculating device would become negligible. Molecular cell computer (MCC) [I] cannot calculate the interaction of a great quantity of different molecules, using the equations of quantum mechanics because the expense of the (price of action) would be very large and both MCC and the surrounding world could change.

Cell Physiological Phenomena

[Cell molecular computer. VIII. Possible construction of a molecular memory in biological membranes and principle of minimum expenditures of free energy in recording information].

The principle of minimum expenditure of "price of action" [5] provides in the liquid cell membrane such operative memory which uses for recording information from any receptor (multidigit number) the transmission of an electron with the loss smaller than 250 mev. According to the hypothesis such memory is constructed from equal protein molecules and different lipid addresses for different receptors. It works on Brown collisions, weak interactions between the molecules and capture bonds controlled by MCC with a minimum expenditure of free energ- for the formation and breakage of bonds.

Cell Membrane

[Metabolic synapse. I. Effect of intracellular microinjection of 3'-5'-AMP].

Cyclic 3'-5'-AMP was injected into neurons of Helix pomatia (theta greater than 50 mu) by the current of 10(8) minus 10(9) A. This current was passed from one intracellular electrode to another by means of a photogenerator very well isolated from the ground. The injection of 3'-5'-AMP results in a depolarization and increase of the frequency of spontaneous activity. These changes continue for several seconds after the current is switched off. The intracellular injection of 5'-AMP or 5'-ATP and also extracellular application of 3'-5'-AMP by either the same or tenfold current does not change the spontaneous activity of these neurons.

Animals

[Input and output channels of quantum biocomputers].

It is proposed that "Quantum Molecular" computer of a neuron consists of the cell cytoskeleton serving as calculating media and input ionic channel sending a hypersound signal to observe these media. The sound spreads through the media travelling along microtubules and microfilaments and switching between those via molecular bridges which serve as elementary switches. The whole system works like a wave guiding net connecting input ionic channels (which generate different sound signals) and output ionic channels (which are controlled by the processed sound signals). Thus the output of such systems depends on the input (controlled by synaptic activity) and on the construction and state of these calculating media. We think that the sound waves spreading through different calculating media solve different physical problems. The construction of the calculating part of the cytoskeleton, according to the hypothesis, is different in different neurons. It is defined by special protein which is produced by DNA, RNA and protein molecular word processor (during brain development and, may be, education). We comment on how the existence of an extremal computer produces an impact on physics and mathematics exemplified by the optimality principle as substitution of physical relativity principle for a complex problem.

Brain

[Study of the metabolic synapse. II. Comparison of the effects of cyclic 3',5'-AMP and 3',5'-GMP].

Intracellular microiontoforetic injections of cyclic 3',5'-AMP and cyclic 3',5'-GMP elicit different responses in the same neuron. Drugs were injected by current of 1--10 nA using 3-barrel micropipettes. Unlike cyclic 3',5'-AMP arising the depolarization of the neuron, cyclic 3',5'-GMP usually hyperpolarizes it. An inhibitor of phosphodiesterases, papaverine, increases and prolongates effects of cyclic 3',5'-AMP and cyclic 3',5'-GMP, but in latter case the action of this drug seems to be less.

Animals

[Bioenergetics and proton-electron membrane systems].

Measurements of potential difference on energy producing subcellular particles by the methods of penetrating ions and of association of these particles with the planar membrane are described as well as some other studies of cell electrical energetics in which the author took part.

Chloroplasts

[The effect of various protein kinase inhibitors on the response of snail neurons to the intracellular injection of cAMP].

Drugs preventing cAMP interaction with regulatory subunit of cAMP-dependent protein kinase, tolbutamide and db-cAMP injected into neurons of Helix lucorum decreased the cell response to cAMP, but H-8-a potent inhibitor of this enzyme catalytic subunit did not produce such effect. It is suggested that the neuron electric response to cAMP injection is not caused by protein phosphorylation.

Animals

Cctionic selectivity of bimolecular membranes in the presence of nystatin and amphotericin B.

Ergosterin or 7-dehydrocholesterin-containing artificial membranes are selectively permeable for cations of alkaline metals in aqueous solutions of nistatin and amphotericine B. Membrane permeability changes spontaneously within several tens of minutes from the cation to the anion one. A decrease of temperature, an increase of medium pH or introduction of dimethylsulphoxide into aqueous solution inhibit, while the addition of calcium accelerate this transition.

Alkanes

[Intraneuronal information processing. An increase in sodium and decrease in potassium permeability after injection of cyclic nucleotide and mechanical stimulation of the neuron].

In voltage clamp experiments the ionic permeability mechanism of the neuron soma evoked by the injection of cyclic nucleotides can be estimated only by studying the reversal potential. The value of this potential allows to conclude that permeability is mainly increased by opening potential independent sodium channels. A delay of ionic current evoked by cyclic nucleotides is tenfold less than the time of cAMP diffusion to the membrane. This leads to a hypothesis about the cyclic nucleotide dependent mechanical opening of sodium channels.

Action Potentials