Effect of nociceptive stimulation of signal transmission from low-threshold cutaneous afferents in the somatosensory system

In cats anesthetized with chloralose nociceptive heating of the skin of the foot to 44–60°C led to a two- to fourfold increase in amplitude of primary cortical responses to direct stimulation of neurons of the spinocervical tract receiving information from the heated area of skin, but did not affect primary responses evoked by stimulation of axons of these neurons in the dorsolateral funiculus, and actually inhibited the response to stimulation of the nerve innervating the heated area of skin. Inhibition was accompanied by depolarization of central terminal of low-threshold fibers of this nerve: During heating the amplitude of the antidromic discharges evoked in the nerve by stimulation of its presynaptic endings in the spinal cord was increased two- to threefold. After abolition of presynaptic depolarization with picrotoxin (0.2–0.7 mg/kg, intravenously) or as a result of asphyxia, nociceptive heating acquired the ability to facilitate primary responses arising as a result of stimulation of the nerve also. The amplitude of the responses was increased under these circumstances by 3–20 times. It is concluded that acute nociceptive stimulation causes such powerful presynaptic inhibition of impulse transmission from low-threshold fibers of the cutaneous nerve that it virtually abolishes the facilitating effect of nociceptive impulses on sensory neurons of the spinal cord. It is suggested that it is this inhibitory mechanism which prevents the development of hyperalgesia during acute nociceptive stimulation.Institute of General Pathology and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 6, pp. 621–627, November–December, 1981.     

Action of thiamine on different synapses

Thiamine at a concentration of 1×10^–14 to 1×10^–4 M facilitated neuromuscular transmission at the glutaminergic synapse of the crayfish adapter, manifesting as increased amplitude and quantal content of excitatory postsynaptic potentials and raised frequency of miniature excitatory postsynaptic potentials. Thiamine augmented spontaneous electrical activity and the amplitude of synaptic potentials in the longitudinal muscle of guinea pig taenia coli. It was found from studying the effects of thiamine on the membrane potential of rat brain synaptosomes that its presynaptic action is brought about by depolarization of the nerve terminal membrane. Interaction between thiamine and the nerve endings was described by a Hill coefficient of 0.22–0.30, indicating that it has several binding sites within the structure of the receptor concerned.A. V. Palladin Institute of Biochemistry, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 5, pp. 621–629, September–October, 1986.     

Calcium-activated potassium conductance in presynaptic terminals at the crayfish neuromuscular junction

Membrane potential changes that typically evoke transmitter release were studied by recording intracellularly from the excitor axon near presynaptic terminals of the crayfish opener neuromuscular junction. Depolarization of the presynaptic terminal with intracellular current pulses activated a conductance that caused a decrease in depolarization during the constant current pulse. This conductance was identified as a calcium-activated potassium conductance, gK(Ca), by its disappearance in a zero-calcium/EGTA medium and its block by cadmium, barium, tetraethylammonium ions, and charybdotoxin. In addition to gK(Ca), a delayed rectifier potassium conductance (gK) is present in or near the presynaptic terminal. Both these potassium conductances are involved in the repolarization of the membrane during a presynaptic action potential.     

Further Study of the Relationship between Pre- and Postsynaptic Potentials in the Squid Giant Synapse

The minimal presynaptic depolarization (MPD) for producing a detectable postsynaptic potential (PSP) was lower than 25 mv in normal or tetrodotoxin (TTX)-containing seawater. The MPD was about 10 mv when a small amount of tetraethylammonium ions (TEA) was injected into the presynaptic terminal. Application of linearly increasing depolarizing current to the normal presynaptic terminal at times produced a PSP before a presynaptic spike was evoked; the rate of rise of the resulting PSP was much slower than that of a PSP triggered by the normal presynaptic spike. A brief depolarizing pulse that preceded the presynaptic spike in normal seawater or the initial transient presynaptic depolarization in TTX decreased the PSP. It increased the PSP when it was applied during the spike or initial transient depolarization. Hyperpolarizing pulses had the reverse effect. The Off-PSP was also modified by inserting pulses at an initial part of the recovery phase of the strong presynaptic depolarization. These results indicate further that increases in Na⁺ and K⁺ conductance during presynaptic spike activity are not a requirement for transmitter release; the rate of release of transmitter can be controlled by electrical manipulation of the presynaptic terminal; there is a superficial correspondence between the time courses of presynaptic depolarization and the resulting PSP. Thus presynaptic depolarization appears to be only the first step in the series of events constituting excitation-transmitter release coupling. It may not be a necessary step for the release mechanism.     

Crayfish motor nerve terminal's response to serotonin examined by intracellular microelectrode

Measurements of resting potential and action potential in presynaptic branches of the excitatory motor axon to the crayfish opener muscle were made with intracellular microelectrodes during application of serotonin (10(-9)-10(-3) M). A 5-min exposure to 10(-6) M serotonin produced enhancement of excitatory junction potentials (EJPs) lasting about 1 h. The membrane potential of the presynaptic terminal was depolarized by about 5 mV; the depolarization subsided within 1/2 h. Concomitant reduction in amplitude of the presynaptic action potential, not accompanied by spike broadening, was observed. The presynaptic depolarization, and the enhancement of EJPs, were dependent on the presence of extracellular sodium but not extracellular calcium. A possible mechanism for serotonin's effect involves initial entry of sodium into the nerve terminal, with consequent increased availability of intracellular calcium. The subsequent long-lasting phase of EJP enhancement may result from an additional effect on the metabolism of the nerve terminal.     

Inhibition of spinal reflex responses in the last period of embryogenesis

Some characteristics of spinal reflex reaction inhibition were studied in cat fetuses during the last three weeks of antenatal development. The experiments were conducted on fetuses with intact placental circulation. Restoration of the excitability of the spinal reflex arcs was very slow after stimulation of the dorsal root by a single stimulus. In embryos studied 20 days before birth the full inhibition of reflex responses lasted about 500 msec. Even 2–3 sec after a single stimulation of the afferent fibers the amplitude of the reflex response to the second stimulus was only 30–40% of the control value. It was determined that such long postactivation depression is unrelated to refractoriness or antidromic inhibition. The presence of a prolonged intense depolarization of afferent terminal fibers at these stages suggests a presynaptic inhibition as one of the most probable reasons for the prolonged postactivation depression. Another important factor in the appearance of postactivation depression is probably the morphologic and functional immaturity of synaptic structures. A reciprocal inhibition was observed in cat fetuses on the 10–12th antenatal day. On the basis of these data it is suggested that in embryogenesis presynaptic inhibition considerably precedes that of postsynaptic fibers.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 3, No. 1, pp. 68–75, January–February, 1971.     

Presynaptic depolarization rate controls transmission at an invertebrate synapse

Second-order neurons L1-3 of the locust ocellar pathway make inhibitory synapses with each other. Although the synapses transmit graded potentials, transmission depresses rapidly and completely so that a synapse only transmits when the presynaptic terminal depolarizes rapidly. The rate at which a presynaptic neuron depolarizes determines the rate at which a postsynaptic neuron hyperpolarizes, and neurotransmitter is only released during a fixed 2 ms long period. Consequently, the amplitude of a postsynaptic potential depends on the rate rather than the amplitude of a presynaptic depolarization. Following a postsynaptic potential, a synapse recovers from depression over about a second. The synapse recovers from depression even if the presynaptic terminal is held depolarized.     

Correlation of Transmitter Release with Membrane Properties of the Presynaptic Fiber of the Squid Giant Synapse

Depolarization of the presynaptic terminal by current produced a postsynaptic potential (PSP) which increased with increasing presynaptic polarization and then reached a plateau. Iontophoretic injection of tetraethylammonium ions (TEA) into the presynaptic axon near the terminal produced a prolonged presynaptic spike. The resulting PSP is increased in size and its time course closely followed that of the presynaptic spike. The presynaptic fiber no longer exhibited rectification and strong depolarizations revealed that the PSP reached a maximum with about 110 mv depolarization. Further depolarization produced a decrease in PSP amplitude and finally transmission was blocked. However, a PSP then always appeared on withdrawal of the depolarizing current. Under the conditions of these experiments, the PSP could be considered a direct measure of transmitter release. Bathing the TEA-injected synapse with concentrations of tetrodotoxin (TTX) sufficient to block spike activity in both pre- and postsynaptic axons did not greatly modify postsynaptic electrogenesis. However, doubling TTX concentration reversibly blocked PSP. Thus the permeability changes to Na and K accompanying the spike do not appear necessary for transmitter release. Some other processes related to the level of presynaptic polarization must be involved to explain the data. The inhibition of transmitter release by strong depolarizations appears to be related to Ca action. A membrane Ca current may also be necessary for normal transmitter release.     

Effect of carbachol on miniature end-plate potentials and currents of rat skeletal muscle

Experiments on rats showed that carbachol (10 µM) appreciably quickens miniature end-plate potentials in the soleus muscle kept in medium with potassium chloride concentration increased to 13 mM. Potentiation of spontaneous mediator release also took place when the membrane potential of the muscle fibers was clamped at the level of the potassium equilibrium potential. It is concluded that the presynaptic action of carbachol on synaptic liberation of acetylcholine from motor nerve endings is unconnected with depolarization of the postsynaptic membrane but takes place as a result of the direct effect of the mimetic on motor nerve endings.S. V. Kurashov Medical Institute, Ministry of Health of the RSFSR, Kazan'. Translated from Neirofiziologiya, Vol. 14, No. 2, pp. 185–189, March–April, 1982.     

Mechanism of inhibition following reflex discharge in spinal cord interneurons

Using the method of microelectrode (intracellular and extracellular) recording, the mechanism of inhibition following reflex discharge in interneurons of the lumbosacral section of the spinal cord of cats on activation of cutaneous and high-threshold muscle afferents was studied. It was shown that the postdischarge depression of the reflex responses 10–20 msec after the moment of activation of the neuron is due to afterprocesses in the same neuron and presynaptic pathways. The depression of spike potentials from the 20th to the 100th msec is produced by inhibitory postsynaptic potentials (IPSP). During the development of IPSP the inhibition of spike potentials can be due to both a decrease of the depolarization of the postsynaptic membrane below the critical threshold and a decrease of sensitivity of the cell membrane to the depolarizing action of the excitatory postsynaptic potential (EPSP). At intervals between the stimuli of 30–100 msec the duration of EPSP after the first stimulus does not differ from that after the second stimulus. Hence, it is suggested that the presynaptic mechanisms do not play an essential part in this type of inhibition of interneurons. The inhibition following the excitation favors the formation of a discrete message to the neurons of higher orders.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 2, No. 1, pp. 3–9, January–February, 1970.     

Functional organization of mechanisms of presynaptic inhibition induced by stimulation of cutaneous afferents

Changes in the N₁-component and P-phase of the dorsal surface potential (DSP) of the spinal cord evoked by test stimulation of the posterior tibial nerve after conditioning stimulation of the sural nerve were investigated in anesthetized cats. The test responses were inhibited if stimulation was applied at short intervals. They then recovered to some extent, but after 1.8–2.2 msec, a further prolonged period of inhibition began. The initial inhibition was connected with occlusion of synaptic action, and the subsequent prolonged inhibition with the development of presynaptic inhibition. The latent periods of prolonged inhibition of the N₁-component and P-phase of the DSP (2 msec) were almost exactly identical, and the curves showing the diminution of the initial occlusion of these components were very similar. The results demonstrate that presynaptic inhibition of the interneurons generating the N₁-component of the DSP and of cells of the substantia gelatinosa which participate in depolarization of the presynaptic terminals of the cutaneous afferents is due to the action of depolarizing systems with similar temporal characteristics.Dnepropetrovsk State University. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 510–515, September–October, 1972.     

Neurotrophic control of the transmembrane Cl− pump in mammalian muscle fibers

Resting membrane potential of both innervated and denervated rat diaphragm muscle fibers was investigated when the concentration of potential-producing ions was changed in the external fluid and following treatment with furosemide. It was found that equilibrium potential ( ) equalled resting potential level in innervated muscle for Cl^–, but shifts to more positive values compared with resting membrane potential following section of the nerve. Furosemide retards development of post-denervation depolarization of the muscle membrane. It is deduced that trophic influences originating from the motor nerve activates the furosemide-sensitive Cl^– influx system, leading to raised intracellular concentration of Cl^–, a shift in (E_Cl) and depolarization of the muscle membrane.S. V. Kurashov Medical Institute, Minsitry of Health of the RSFSR, Kazan'. Translated from Neirofiziologiya, Vol. 19, No. 6, pp. 766–771, November–December, 1987.     

Presynaptic dense bars at neuromuscular synapses of the lobster,Homarus americanus

Summary The threedimensional ultrastructure of presynaptic dense bars was examined by serial section electron microscopy in the excitatory neuromuscular synapses of the accessory flexor muscle in the limbs of larval, juvenile, and adult lobsters. The cross-sectional profile of the dense bar resembles an asymmetric hourglass, the part contacting the presynaptic membrane being larger than that projecting into the terminal. The bar has a height of 55–65 nm and varies in length from 75–600 nm. In its dimensions it resembles the dense projections in the synapses of the CNS of insects and vertebrates. The usual location of these dense bars is at well defined synapses, though a few are found at extrasynaptic sites either in the axon or terminal. In the latter case the bars are close to synapse-bearing regions, particularly in the larval terminals, suggesting that the extrasynaptic bars denote early events in synapse formation. In all cases the bars are intimately associated with electron lucent, synaptic vesicles located on either side, in the indentation of its hourglass-shaped cross sectional profile. The vesicles occur along the length of the bar and contact the presynaptic membrane. Consequently the dense bar may serve to align the vesicles at the presynaptic membrane prior to exocytosis. A similar role has been suggested for the presynaptic dense bodies at the neuromuscular junction of the frog, where synaptic vesicles form a row on either side of this structure.Supported by Muscular Dystrophy Association of Canada and NSERCC. Generous use of laboratory facilities at Woods Hole was provided by the late Fred Lang     

Participation of nonsegmentary neurons of the spinal cord in execution of presynaptic control

Experiments were carried out on cats six days after complete transection of the spinal cord. Cord dorsum potentials (CDP) were recorded in the vicinity of the third lumbar segment during stimulation of the isolated dorsolateral funiculus (DLF). The CDP consist of a rapid monophasic potential (which apparently reflects antidromic excitation of the cells of Clarke's column) and two subsequent slow negative waves, which are replaced by a long positive oscillation. In form, time characteristics, and behavior during thythmic stimulation, this potential differs considerably from the CDP recorded during stimulation of the afferent nerves. The presence of a positive phase of the CDP indicates that stimulation of the DLF evokes primary afferent depolarization (PAD). Stimulation of the DLF causes inhibition of the CDP evoked by stimulation of the afferent nerve. The time course of this inhibition corresponds to the time course of presynaptic inhibition. It is demonstrated that stimulation of the afferent nerve (n. femoralis) inhibits slow components of the CDP evoked by stimulation of the DLF. This inhibition reaches a maximum at the 16th millisecond; its duration exceeds 300 msec. Stronger and more prolonged inhibition of the same components is observed when both the conditioning and the testing stimuli are administered to the DLF. Since primary afferents do not take part in CDP emergence during stimulation of the DLF, it may be hypothesized that the observed inhibition develops as a result of depolarization of interneuron axon terminals.Dnepropetrovsk State University. Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 520–527, September–October, 1970.     

Ca2+-dependent Cl− efflux in tonoplast-free cells ofNitellopsis obtusa

Summary In order to demonstrate the presence of a Ca²⁺-activated Cl^–-channel in theNitellopsis plasmalemma, tonoplast-free cells were prepared and their intracellular Ca²⁺ concentration was modified by internal perfusion. An increase in the Ca²⁺ concentration caused a large Cl^– efflux with a concomitant depolarization of the membrane potential. These changes were for the most part reversible. The critical Ca²⁺ concentration was about 4.0 m. Neither the Cl^– efflux nor the membrane depolarization showed a time-dependent inactivation. A Cl^–-channel blocker, A-9-C (9-anthracenecarboxylic acid) reduced both the Cl^– efflux and the magnitude of the membrane potential depolarization. A small increase in the intracellular Ca²⁺ concentration, which is caused by membrane excitation of tonoplast-free cells is not sufficient to activate this Ca²⁺-dependent Cl^–-channel.     

Model feedback mechanism between horizontal cells and photoreceptors of the vertebrate retina

A model with nonlinearity of the photoreceptor presynaptic membrane as its important distinguishing feature was created on the basis of the hypothesis that feedback between the horizontal cells and photoreceptors is effected by a current generated by the subsynaptic membrane of the horizontal cells and leaking partly into the photoreceptors. Measurements with the model also reproduced experimental observations such as depolarization of the cone during hyperpolarization of the horizontal cell in response to the showing of a ring of light or passage of an electric current, and also certain special features of the current-voltage curves of the cones.Institute of Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 9, No. 1, pp. 86–94, January–February, 1977.     

Effect of polarization of horizontal cells of the pike retina on spread of their electrical potentials

The spread of electrical responses over the layer of horizontal cells of the pike retina was investigated at different levels of their membrane potential varied by application of a steady current. Depolarization of the membrane, accompanied by an increase in its resistance, led to an increase in its time constant and length constant, so that electrical waves spread further over the layer of horizontal cells. The effect of polarization was thus due to the nonlinear membrane properties of the horizontal cells, i.e., to the increase in their resistance on depolarization and its decrease on hyperpolarization. In some cases this nonlinearlity was manifested as a special type of regeneration: the same strength of steady current crossing the membrane of the horizontal cells corresponded to two stable levels of the membrane potential. The role of various factors (changes in resistance of the extrasynaptic and subsynaptic membranes of the horizontal cells, the presynaptic effect of the current) determining the spread of the potentials over the horizontal cells under natural conditions during photic stimulation is discussed.Institute of Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 4, No. 1, pp- 90–96, January–February, 1972.     

Effects of pyrocatechol on neuromuscular transmission

Effects of pyrocatechol on neuromuscular transmission were studied both in the frog pectoral-cutaneous muscle and in the mouse phrenic-diaphragmatic preparation by means of extracellular microelectrode recording of synaptic signals. Pyrocatechol applied in a concentration of 0.05 mM increased the frequency of miniature end-plate currents (MEPC) and the amplitude of end-plate current (EPC) by increasing its quantum content. Pyrocatechol also increased the duration of presynaptic response. When voltage-dependent potassium channels had been blocked, pyrocatechol affected neither the EPC quantum content nor the duration of presynaptic response. It is suggested that the pyrocatechol-induced enhancement of transmitter release results from modulatory effects of pyrocatechol on voltage-dependent potassium current in the membrane of a nerve terminal.Neirofiziologiya/Neurophysiology, Vol. 25, No. 6, pp. 405–408, November–December, 1993.     

Synaptic processes in smooth muscles

Synaptic potentials of smooth muscles of the gastrointestinal tract arising in response to intramural stimulation were studied by intracellular recording of potentials and the sucrose gap method. The results showed that muscarinic cholinergic neuromuscular transmission in smooth-muscle cells of the gastrointestinal tract is purely excitatory. This transmission is most marked in the fundal part of the stomach. Adrenergic control of motor activity is manifested as excitation and inhibition of smooth muscles. Relations between these phenomena differ in different parts of the gastrointestinal tract. Depression of inhibitory adrenergic effects by apamin discloses excitation of smooth muscles which is not found under ordinary conditions. Like its inhibitory action, the excitatory action of noradrenalin is exerted as a result of activation of -adrenoreceptors. Nonadrenergic synaptic inhibition, which is more effective than adrenergic, is found in smooth-muscle cells of the circular layer of all parts of the gastrointestinal tract studied. Inhibitory postsynaptic potentials consists of two components: a first fast, and a second slow. Apamin blocks mainly the first phase of the synaptic response. During inhibition of nonadrenergic inhibitory postsynaptic potentials by apamin, noncholinergic synaptic excitation resistant to the action of blockers of cholinergic, adrenergic, and serotoninergic transmission is found in smooth muscles of the cecum. It is complex in character in this part of the intestine: an initial excitatory postsynaptic potential and a slow late depolarization wave. In smooth-muscle cells of other parts noncholinergic excitation is manifested only as a slow depolarization wave. The following types of synaptic influences of the autonomic nervous system on smooth-muscle cells of the gastrointestinal tract are therefore postulated: nonadrenergic excitatory, both cholinergic and noncholinergic; nonadrenergic inhibitory, adrenergic excitatory and adrenergic inhibitory, and also presynaptic modulation of neuromuscular transmission.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 307–319, May–June, 1984.     

Some effects of prolonged polarization on membrane currents in bullfrog atrial muscle

Summary Bullfrog atrial trabecula were voltage-clamped using a double-sucrose-gap method. Step depolarization produced a slowly changing outward current which was studied by analyzing the current tail produced by repolarization. The initial phase of the current tail (time constant 0.1 to 0.7 sec at –60 mV) had a reversal potential which depended upon the duration and magnitude of the preceding depolarization. Calculations based on trabecular geometry and the behavior of the currents in high external potassium suggest that part of the current tail reflects a restoration to a lower steadystate concentration of external potassium which had accumulated in narrow clefts between cells during the preceding depolarization. Step hyperpolarization produced a declining inward current (time constant 0.3 sec at –100 mV) which can be explained on the basis of a depletion of potassium from these intercellular clefts (about 0.5% of the trabecular volume).