The actions of the nootropes noopept and piracetam on depression of the acetylcholine-induced current in a cellular analog of habituation were studied. Mathematical modeling of experimental curves and their analysis using previously obtained results on the effects of inhibitors of different protein kinases and protein phosphatases on acquisition of depression of the acetylcholine-induced current in a cellular analog of habituation clarified the intracellular processes and targets on which these agents act.
Using electrophysiology, the effect of nicotinic acetylcholine receptor (nAChR) ligands on acetylcholine-induced depolarization in the neurons of Helix lucorum snail was studied. It was found that the α-conotoxin PnIA [R9, L10], a selective antagonist of α7 nAChR, and α-cobratoxin (antagonist of α7 and muscle-type nAChR) suppressed neuronal depolarization. Fluorescence microscopy showed staining of the neurons with fluorescently labeled α-bungarotoxin; this staining was reduced by pretreatment with α-cobratoxin. Induced depolarization was also suppressed by α-conotoxin RgIA, a selective inhibitor of α9 nAChR. In contrast to Lymnaea stagnalis nAChR, which are weakly sensitive to neurotoxin II and α-conotoxin GI, antagonists of muscle-type nAChR, H. lucorum receptors were most effectively inhibited by these antagonists. The results obtained, as well as the previously found sensitivity of the receptors studied in this work to muscarinic receptor ligands, indicate an unusual atypical pharmacological profile of H. lucorum nAChR.
The heat exchange process of moist sodium carboxymethyl cellulose is studied. The method for determining the thermal conductivity coefficient of a moist disperse material is developed. The thermophysical properties of sodium carboxymethyl cellulose are determined. The influence of moisture content and density of the material on its thermal conductivity coefficient is studied. An empirical equation is derived by processing the experimental data to calculate the thermal conductivity coefficient of sodium carboxymethyl cellulose at different densities of the moist material.
The nootropic agents noopept and piracetam alter the amplitudes of acetylcholine-induced influx currents (ACh currents) in command neurons in the common snail. Both compounds have cholinopositive activity. The dose curve of the actions of noopept is bell-shaped, while the piracetam dose-response curve in the range of physiological concentrations shows a monotonous rise. Noopept increases the ACh current at low concentrations (10–10–10–8 M), while piracetam acts at significantly higher concentrations (starting from 10–4 M). The magnitudes of the maximal cholinopositive effects of noopept and piracetam (in the range of physiological concentrations) were identical, while the concentrations of nootropic drugs at which they were reached differed by seven orders of magnitude. The half-maximal concentration (EC50) of noopept was 10–10 M and that of piracetam was 10–3 M. The mechanisms of the cholinopositive actions of these drugs are discussed.
Abstract—Possible causes of the positive modulating effect of noopept (in a concentration range of 0.1 to 10 nM) on the amplitude of the acetylcholine-induced input current are analyzed using a developed mathematical model. The results revealed that the calculated and experimental current curves coincide when the number of nicotinic acetylcholine receptors on the neuron membrane is increased or the efficiency of muscarinic acetylcholine receptors is changed.
Nootropic drugs (Noopept and Piracetam) change amplitude of the inward acetylcholine-induced current (ACh-current) in command Helix neurones. Both drugs show cholinopositive action. A dose curve of influence of the Noopept is bell-shaped, and curve dose-effect in the field of physiological concentration of Piracetam is monotonously increasing. Noopept increases ACh - current at low concentrations (10(-10) - 10(-8) M), and Piracetam made it at much high concentrations (since 10(-4) M). Maximal cholinopositive effects of Noopept and Piracetam (in the field of physiological concentrations) are identical while concentration of nootropic drugs at which they are reached, differ on 7 orders. Semi-maximal concentration (EC50) of the Noopept was 10(-10) M, and EC50 of Piracetam was 10(-3) M. The conclusion was made about the mechanisms of cholinopositive effect of drugs.
Na + /K + -pump is an electrogenic transmembrane ATPase located in the outer plasma membrane of cells. The Na + /K + -ATPase pumps 3 sodium ions out of cells while pumping 2 potassium ions into cells. Both cations move against their concentration gradients. This enzyme’s electrogenic nature means that it has a chronic role in stabilizing the resting membrane potential of the cell, in regulating the cell volume and in the signal transduction of the cell. This review will mainly consider the role of the Na + /K + -pump in neurons, with an emphasis on its role in modulating neurotransmitter receptor. Most of the literature on the modulation of neurotransmitter receptors refers to the situation in the mammalian nervous system, but the position is likely to be similar in most, if not all, invertebrate nervous systems.
The presynaptic mechanism of short-term plasticity of synaptic transmission was studied by analyzing the effects of rhythmic orthodromic stimulation of the intestinal nerve, inducing short-term potentiation of evoked EPSP, on spontaneous EPSP in defensive behavior command neurons in the common snail. Rhythmic stimulation had no effect on the amplitude of spontaneous EPSP but led to significant increases in the number of spontaneous EPSP. The increase in the frequency of spontaneous EPSP suggested a role for a presynaptic mechanism in the short-term potentiation of synaptic transmission. This presynaptic mechanism may include a decrease in the action potential generation threshold (AP) in presynaptic neurons, which leads to an increase in the proportion of spontaneously active neurons and, thus, supports an increase in the number of spontaneous presynaptic AP.
Microtubule motor proteins – kinesins and dyneins – play an important role in intracellular transport. Impairments to axon transport can influence neurotransmitter release and short-term presynaptic plasticity. Impairments to dendritic transport, particularly recycling of synaptic receptors, affect postsynaptic plasticity. This review seeks to follow the link between microtubule motor proteins and the mechanisms of synaptic plasticity from the point of view of their involvement in transporting proteins and organelles, where their role in the mechanisms of synaptic plasticity has been demonstrated.
We have studied how various drugs increasing the rate of nicotinic acetylcholine receptors (nAChRs) lateral diffusion affect the depression of ACh-induced current in land snail Helix lucorum neurons responsible for defensive behavior. The acetylcholine (ACh) iontophoretic application protocol imitated the behavioral habituation protocol for the intact animal. We found that the drugs decreasing cholesterol level in cell membranes as methyl-β-cyclodextrin 1 mM and Ro 48-8071 2 µM, and polyclonal antibodies to actin-binding proteins as spectrin 5 µg/ml and merlin 2.5 µg/ml have changed the dynamic of ACh-current depression. The nAChRs lateral diffusion coefficient was obtained by fluorescence recovery after photobleaching. A curve fitting model specially created for analysis of short-term choline sensitivity depression in snail neurons helped us evaluate separately the contribution of nAChRs lateral diffusion, their endocytosis and exocytosis to observed effects during electrophysiological experiments. Taken together, we hypothesize that nAChRs lateral diffusion plays an important role in the cellular correlate of habituation in land snail Helix lucorum neurons.
The experimental relationship between the paired-pulse ratio of acetylcholine-induced inward currents in the command neurons of Helix lucorum and the interval between application of a neurotransmitter was analyzed using the method of paired-pulse stimulation. A mathematical model that takes the membrane and intracellular localization of receptors, their lateral diffusion, and endocytosis and exocytosis depending on the intracellular processes into account was used to study this dependence. Our results have shown that membrane receptor endocytosis is the main process that determines the type of this relationship. The effects of exocytosis and lateral diffusion of membrane receptors on this relationship were studied. The parameters of an existing mathematical model were further clarified.
To develop the presynaptic mechanism of the short-term plasticity of synaptic transmission the influence of the rhythmical orthodromic stimulation of intestinal nerve on the spontaneous excitatory postsynaptic potentials (EPSPs) have been analyzed in the command neurons of the defensive behavior of land snail Helix lucorum. It was shown early that the tetanic stimulation induced the short-term potentiation of evoked EPSPs. The rhythmical stimulation did not influence the amplitude of spontaneous EPSPs, but considerably increased their number. Discovered augmentation of the frequency of spontaneous EPSPs makes it possible to assume the participation of presynaptic mechanism in the short-term potentiation of synaptic transmission. The presynaptic mechanism can include reduction in the thresh- old of action potentials (APs) generation in the presynaptic neurons, which will lead to an increase in the fraction of spontaneous active neurons and, correspondingly, it will increase the number of spontaneous presynaptic APs.