PubMed Health⌕ Search

Biomedical subjects

P G Kostiuk

Publications and source records attributed to P G Kostiuk.

At least 19 recordsLinked to original sources

[Calcium ions and the nervous system plasticity].

The nervous system is different from all other systems of the organism by extreme flexibility of the structural and functional properties of its elements. This unique feature of the nervous system can be best described as plasticity in a broad sense of the word. All forms of plastic changes in the nervous system functioning have common basic mechanisms, the changes at the free Ca2+ cytosol ions being the most important one. These "calcium signals" trigger an extremely complicated intracellular machinery capable of controlling the structural and functional properties of the nervous system during the whole life span. This review summarises data on the intracellular Ca2+ ions mechanisms controlling the developmental plasticity of neuronal elements, synaptic plasticity of the mature nervous system, and the decline of plastic capabilities with ageing.

Aging↗

[Endoplasmic reticulum and mitochondria as elements of mechanism of intracellular signaling in neurons].

The temporal and spatial characteristics of a transitory increase in free Ca2+ ("calcium signals") concentration were determined in various types of the mice and rat neurones. Intracellular structures: endoplasmatic reticulum and mitochondria, were shown to play a major part in formation of these signals, the structures being able to absorb the Ca2+ ions from cytosol and release them back. The contribution of these processes proves rather varying depending on internal organisation and functional assignment of a neurone.

Animals↗

[Nikolaĭ Nikalaevich Sirotinin and his school].

In a brief review of 50-year scientific activity of professor N. N. Sirotinin and his students the authors emphasize that this broad-minded scientist contributed to development of such disciplines as microbiology, pathophysiology, high-altitude, aerospace medicine. However, his main goal was evolution of reactivity and resistance, approaches to perfection of human health and performance. Much attention was paid to effects of low partial oxygen pressure on human and animal body, to hypoxic states of different origin. Methods of hypoxytherapy and hypoxic training are widely used in Russia and abroad. The contribution of academician N. N. Sirotinin to modern pathophysiology, high-altitude and aerospace physiology, internal and sport medicine is highly appreciated in Russia.

Aerospace Medicine↗

[Voltage-gated influx ion channels expressed in Xenopus oocytes after the administration of brain mRNA].

Expression of "fast", TTX-sensitive sodium and high-threshold calcium channels in the membrane of Xenopus oocytes following mRNA injection from the rat brain has been detected using two microelectrode voltage clamp technique. Barium current through expressed calcium channels was blocked by 200 mumol/l Cd2+ and was insensitive to D-600 (20 mumol/l) and nitrendipine (50 mumol/l). Expressed barium current was inhibited within 20-40 min by omega-conotoxin, a peptide neurotoxin known to block high-threshold calcium channels of the neuronal membrane, in 1 mumol/l concentration. A steady-state inactivation curve for this current could be fitted by the Boltzmann relation with V1/2 = -50 mV and k = 14 mV. Voltage-dependent and pharmacological properties of calcium channels which appeared in the oocyte membrane following mRNA injection from the mammalian brain resembled most of all those of high-threshold inactivating (HTI- or N-type) calcium channels of neurons in spite they did not demonstrate prominent time-dependent inactivation. Evidences in favour of expressed calcium channels heterogeneity were not obtained.

Animals↗

[Parathyroid hormone stimulation of nerve cell calcium conduction].

Parathyroid hormone (PTH) has been studied for its effect on the voltage-sensitive calcium channels in voltage-clamp experiments on intracellularly perfused snail neurons. A two-stage action of the hormone on the calcium current (Ica) was shown. An initial stage was a short-term one and consisted in an increase of ICa by 7-10%. The second stage developed slowly for 60-70 min, ICa increased twice. The exogenous cAMP and cGMP did not produce such an effect as PTH did. It is suggested that the phosphoinositide pathway mediates the PTH effect.

Animals↗

[The effect of cAMP on the calcium currents of mollusk neurons possessing different sensitivities of their calcium conductance to serotonin action].

The action of cAMP (100 microM) and serotonin (5-HT, 1-10 microM) on the calcium current (Ica) in intracellularly perfused Helix pomatia neurons was studied with voltage clamp method. Three types of 5-HT-induced changes in the calcium current were observed in different cells: reversible blockade, increase and no changes in the current amplitude. Intracellular introduction of exogenous cAMP (100 microM) affected Ica only in cells with the stimulatory effect of 5-HT; cAMP-induced increase in the current amplitude was not additive to that elicited by 5-HT while both of these effects were similarly potentiated by cyclic nucleotide-phosphodiesterase inhibitor. The data presented show that the stimulatory action of 5-HT on the potential-activated calcium current is mediated by an increase in intracellular cAMP. Existence of two types of calcium channels differing in their dependence on cAMP metabolism is suggested in the snail neurons. The presence of the cAMP-dependent calcium channels seems to correlate with the existence of the definite type of 5-HT receptors in the cell membrane. A new approach to the investigation of isolated neurons is suggested: their functional identification.

Animals↗

[Action of forskolin on the calcium current in the membrane of nerve cells in mollusks].

The action of forskolin, adenylate cyclase activator, on the calcium inward current was studied on intracellularly perfused nonidentified snail neurons. Extracellular application of 5-20 mumol/l of forskolin was shown to cause about 20% increase of the calcium current amplitude and this confirms the previous suggestion that the stimulation of the cellular synthesis of cAMP leads to enhancement of the calcium current through the cell membrane.

Animals↗

[Single channels of low and high-threshold calcium channels of the membrane of sensory neurons in the mouse].

Single calcium channels of cultured dorsal root ganglion cells from mouse embryos were studied using patch clamp method in its cell-attached configuration. Two types of activity of unitary calcium channels were found. The first one which arose at membrane potentials near--50-40 mV was characterized by unitary current amplitude of 0.37 +/- 0.04 pA with 40 mmol/l Ca2+ in the pipette solution, mean open time of 0.6 ms and intraburst mean shut time of 1.2 ms. It displayed voltage- and time-dependent inactivation. The corresponding values for the second one which required much more positive depolarization to be activated (approximately 0 mV) and did not express noticeable inactivation were: 0.53 +/- 0.04 pA, 0.8 ms and 0.8 ms. It is concluded that the recorded types of unitary activity are associated respectively with low- and high-threshold calcium currents which have been found earlier while studying whole cell currents.

Animals↗

[Kinetic pattern of a model of a calcium channel with 2 conformational states].

A kinetic scheme of the organization of ion-transport processes in the calcium channel is suggested and analytical expressions for mixed current of monovalent and divalent cations are obtained on its basis. This model predicts the reversal potential for the calcium current when intracellular solution contains monovalent cations and the anomalous behaviour of the mixed current of divalent cations depending on the mole fraction.

Calcium↗

[Changes in the ionic mechanisms of the electro-excitability of the somatic membrane of rat sensory neurons during ontogenesis. Distribution of ion channels of the inward current].

Distribution of different types of ionic channels carrying inward currents was studied in the somatic membrane of rat dorsal root ganglion neurons within three age groups: 5-9 days, 45 days and 90 postnatally. The number of neurons whose membrane contained simultaneously four types of inward current channels ("fast" tetrodotoxin-sensitive and "slow" tetrodotoxin-resistant sodium low- and high-threshold calcium one's) was progressively reduced in successive groups. The first group contained 14.5%, the second 5% and the third group 1% of such neurons. These changes were due to disappearance of "slow" sodium and low-threshold calcium channels from the membrane; the number of neurons whose somatic membrane contained only two types of inward current channels ("fast" sodium and high-threshold calcium) has increased, respectively.

Aging↗

[Changes in the ionic mechanisms of the electro-excitability of the somatic membrane of rat sensory neurons during ontogenesis. Density ratios of inward currents].

Correlations between densities of different types of inward currents in the somatic membrane of dorsal root ganglion neurons were studied in three age groups of rats (5-9 days, 45 days and 90 days postnatally). A linear dependence between the densities of high-threshold calcium and slow sodium currents was found. No correlation was observed between the densities of different inward currents in neurons with low-threshold calcium inward current. An inverse dependence was observed between the densities of transmembrane currents in cells having only two types of channels ("fast" sodium and high-threshold calcium ones). Neurons exhibiting slow TTX-resistant sodium and/or low-threshold calcium channels did not show inverse dependence between the densities of "fast" sodium and high-threshold calcium currents.

Aging↗

[Changes in the ionic mechanisms of the electro-excitability of the somatic membrane of rat sensory neurons during ontogenesis. Relation between calcium channels and intracellular metabolism].

A change in the relationship between high-threshold calcium channels and intracellular metabolism of cyclic nucleotides during postnatal development was found in experiments on rat dorsal root ganglion neurons. In the first age group (5-9 postnatal days) intracellular administration of cAMP-ATP-Mg2+ complex has resulted in restoration of the maximal amplitude of high threshold calcium current for 70% of neurons, whereas in the second (45 days) and third (90 days) age groups this effect was observed only in 26% and 10% of neurons, respectively. Kinetic and voltage-dependent characteristics of high-threshold calcium current in these three age groups were identical. The effect of introduction of cAMP-ATP-Mg2+ complex was different for neurons with different combination of inward currents. Neurons which possessed only two types of inward currents--"fast" sodium and high-threshold calcium ones, show no effect. Conventional effect of the intracellular cAMP injection occurred always in neurons which had exhibited a "slow" (TTX-resistant) sodium inward current together with the two main inward currents.

Adenosine Triphosphate↗

[Deactivation of calcium currents in the soma of spinal ganglion neurons after elimination of the depolarizing shift in the membrane potential].

Kinetic and voltage-dependent characteristics of deactivation of calcium inward currents with the removal of membrane depolarization were studied in the somatic membrane of rat dorsal root ganglion neurons by intracellular dialysis technique. The "tail" of low-threshold calcium current could be described reliably by one exponent with time constant tau 1-1.2-1.8 ms at repolarization to --90 mV. The "tail" of the high-threshold calcium current represented a sum of several exponents; the time constant of the main component tau h was in the range of 250-380 microseconds. tau 1 and tau h remained practically unchanged for repolarization potentials in the subthreshold region; however, they increased if it was in the range of potentials at which the corresponding component of the calcium current started to activate. A dependence of tau 1 and tau h on the duration of depolarizing shift was observed. The results obtained are discussed in the framework of a three-level kinetic model of calcium channels.

Animals↗

[Relation between metabolism and the function of ion channels in the nerve cell membrane].

The effect of varying intracellular 3.5-cAMP level on steady-state and voltage-dependent transmembrane ionic currents has been studied on both vertebrate and invertebrate nerve cells. A change in 3.5-cAMP level was achieved either by its direct introduction into the cell or by stimulation or inhibition of the activity of different enzymes of the cyclase system. Intracellular cAMP increase was found to activate a steady-state transmembrane current whose early component is related mainly to the increase of sodium and calcium conductance of the membrane, and a late one to increase of potassium conductance (possibly, activated by Ca2+ influx). The decrease of intracellular cAMP concentration (by intracellular dialysis) results in reduction of the potential-activated inward calcium current, whereas its increase restores the current. Restoration of calcium current can be achieved by activation of cellular adenylate cyclase, inhibition of phosphodiesterase or by direct intracellular introduction of the catalytic subunit of cAMP-dependent protein kinase. The evidence is presented that the observed regulatory effects are mediated through cAMP-dependent phosphorylation of proteins of corresponding ionic channels. The increase of intracellular Ca2+ level closely cooperates with this regulatory metabolic system by activation of a number of its enzymatic processes.

Animals↗

[Calcium ion channels in the cell membrane].

The intracellular perfusion technique rendered isolated neurons a convenient object for studying the Ca channels securing inflow of these ions across the membrane into the cell in excitation. Extensive research showed the Ca channels to pass the cations in the sequence Ba greater than Sr greater than Ca greater than Mg and bind these ions with the aid of a binding compound within the channel. Other cation (Co, Ni, Mn, Cd) which are too closely bound with this compound become competitive blocking agents for the channels. In absence of the bivalent cations in the extracellular space the Ca channels loose their selectivity and allow monovalent cations to pass, the reason for this transformation beeing a disruption between the bound Ca ions and the specific regulating compound within the Ca channels. The channels can exist in two states: conducting and nonconducting. The transition from one state to another is accompanied by an intramembrane transfer of charges ("the gate current"). The statistic kinetics of this transition can be described by means of a modified Hodgkin-Huxley equation. In prolonged depolarization the Ca channels become inactivated due to recurrent blocking effect of the Ca ions penetrating in the cell. Some types of the Ca channels, however, reveal a potential-dependent inactivation analogous to that of the sodium or potassium channels.

Animals↗