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I Parnas

Publications and source records attributed to I Parnas.

At least 19 recordsLinked to original sources
PubMed1992

Neurotransmitter release: facilitation and three-dimensional diffusion of intracellular calcium.

In order to account for the time courses of both evoked release and facilitation, in the framework of the Ca2+ hypothesis, Fogelson and Zucker (1985, Biophys. J. 48, 1003-1017) suggested treating diffusion of Ca2+, once it enters through the Ca2+ channels, as a three-dimensional process (three-dimensional diffusion model). This model is examined here as a refined version of the "Ca(2+)-theory" for neurotransmitter release. The three-dimensional model was suggested to account for both the time course of release and that of facilitation. As such, it has been examined here as to its ability to predict the dependence of the amplitude and time course of facilitation under various experimental conditions. It is demonstrated that the three-dimensional diffusion model predicts the time course of facilitation to be insensitive to temperature. It also predicts the amplitude and time course of facilitation to be independent of extracellular Ca2+ concentration. Moreover, it predicts that inhibition of the [Na+]o in equilibrium with [Ca2+]i exchange does not alter facilitation. These predictions are not upheld by the experimental results. Facilitation is prolonged upon reduction in temperature. The amplitude of facilitation declines and its duration is prolonged upon increase in extracellular Ca2+ concentration. Finally, inhibition of the [Na+]o in equilibrium with [Ca2+]i exchange prolongs facilitation but does not alter the time course of evoked release after an impulse.

Animals↗
PubMed1991

Effects of intra-axonal injection of Ca2+ buffers on evoked release and on facilitation in the crayfish neuromuscular junction.

Ca2+ buffers were injected into the excitatory axon of the crayfish opener muscle. The magnitude and time course of evoked release and of facilitation were measured. EGTA (on-rate about 10(6) M-1S-1) had no effect on evoked release but reduced facilitation. BAPTA and nitr-5, buffers with similar Kd's but faster on-rates, reduced both evoked release and facilitation. However, these buffers had no effect on the time course of evoked release. These results show that fast Ca2+ buffers reduce the Ca2+ transient associated with evoked release and also the level of residual Ca2+ involved in facilitation. However, Ca2+ buffering is not the mechanism which controls the time course of release.

Animals↗
PubMed1991

Evoked phasic release in frog nerve terminals obtained after block of Ca2+ entry by Cd2+.

Cutaneous pectoris muscles of frogs were isolated, mounted in a chamber and superfused with Ringer's solution. With a macro-patch-clamp electrode placed on a section of a motor nerve terminal, quantal synaptic currents were elicited by depolarizing pulses and recorded. The electrode tip and the section of the terminal recorded from were perfused rapidly by Ringer's solution alone or containing 20-500 microM Cd2+ to block Ca2+ inflow. Separate superfusion of the muscle and the rest of the terminal with normal or elevated Ca2+ Ringer's solution provided a sufficiently high resting Ca2+ concentration in the terminal even when Ca2+ was blocked by Cd2+. The depolarization level of maximal Ca2+ inflow into the terminal was found by measuring maximal test pulse facilitation, Fc. In control solution as well as in the case of Cd2+ block, the rate of phasic release after depolarizing pulses rose further when depolarization was increased past the level of Fc, and reached a saturation level which was maintained at estimated depolarizations up to +200 mV. Block of Ca2+ inflow by Cd2+ decreased release substantially, but did not suppress it. The depression of release was greater in the range of large Ca2+ inflow (around Fc) than for very large depolarizations. The time course of phasic release was unaltered by blockage of Ca2+ inflow. It is concluded that Ca2+ inflow contributes to the promotion of evoked release only in the depolarization range in which Ca2+ inward current is large.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Synaptic transmission in decentralized axons of rock lobster.

Axons of the lobster deep abdominal extensor muscles were cut, and the resulting effects on their synaptic properties were observed. Decentralized axons continued to conduct action potentials and to release transmitter for at least a year after the cut. In controls, the single quanta were brief, and their decay phase could be fit by a single exponent, with a time constant of about 2 msec. Quanta of "cut axons" were slower, and their decay phase could not be fit by a single exponent. At midamplitude, the duration of the cut-axon quanta varied between 1.6 and 5.8 msec, as opposed to 0.6-2.8 msec in controls. Synaptic delay histograms were taken as a measure of time course of evoked release. In controls, evoked release lasted less than 10 msec at 14 degrees C. In cut axons, release lasted up to 10 times longer. The duration of release was not affected by tetrodotoxin, membrane depolarization, or hyperpolarization. It appears that the basic mechanism that controls the time course of evoked release is altered in degenerating terminals.

Action Potentials↗
PubMed1990

Blockage of synaptic release by brief hyperpolarizing pulses in the neuromuscular junction of the crayfish.

1. Synaptic currents were evoked at the neuromuscular junction of the deep extensor abdominal muscle of the crayfish by direct depolarization of motor nerve endings. 2. Quantal content and time course of neurotransmitter release were determined from delay histograms of unitary release events recorded with a macropatch clamp technique. 3. Synaptic facilitation was elicited by pairing depolarizing pulses at intervals ranging from 10 to 200 ms. At 14 degrees C the duration of facilitation was about 50 ms. Reducing activity of the Nao(+)-Cai2+ exchange by lowering [Na+]o by 50% resulted in prolonged facilitation, which lasted approximately 150 ms. 4. Normalized synaptic delay histograms at normal [Na+]o and 50% [Na+]o were the same for the first and the facilitated second response, indicating that activity of the Na(+)-Ca2+ exchange does not determine the time course of release. 5. The application of a hyperpolarizing post-pulse after the first depolarizing stimulus reduced release and altered its time course to a similar extent both in normal and in 50% [Na+]o. However, it did not affect the level and the time course of release of the facilitated response. 6. A hyperpolarizing post-pulse given after the first and second pulses of a pair reduced release to the same extent for the two depolarizing pulses. 7. These results indicate that whereas manipulations thought to increase [Ca2+]i (i.e. reducing activity of the Nao(+)-Cai2+ exchange or facilitation) affect the quantal content, they do not influence the time course of release. However, changes of membrane potential do affect the quantal content, and more importantly the time course of release, thus suggesting a contributory role of membrane potential in the control of synaptic release.

Action Potentials↗
PubMed1989

Membrane depolarization evokes neurotransmitter release in the absence of calcium entry.

The discovery that Ca2+ is necessary for the release of neurotransmitter, the primary means by which nerve cells communicate, led to the calcium hypothesis of neutransmitter release, in which release is initiated after an action potential only by an increase in intracellular Ca2+ concentration near the release sites and is terminated (1-2 ms) by the rapid removal of Ca2+. Since then, the calcium-voltage hypothesis has been proposed, in which the depolarization of the presynaptic terminals has two functions. First, in common with the calcium hypothesis, the Ca2+ conductance is increased, thereby permitting Ca2+ entry. Second, a conformational change is induced in a membrane molecule that renders it sensitive to Ca2+, and then binding of Ca2+ to this active form triggers release of neurotransmitter. When the membrane is repolarized, the molecule is inactivated and release is terminated, regardless of the local Ca2+ concentration at that moment. This hypothesis, in contrast to the calcium hypothesis, accounts for the insensitivity of the time course of release to experimental manipulations of intracellular Ca2+ concentration. Furthermore, it explains rapid termination of release after depolarization, even though Ca2+ concentration may still be high. Here we describe experiments that distinguish between these two hypotheses and find that our results support the calcium voltage hypothesis.

Action Potentials↗
PubMed1989

Long-term survival of decentralized axons and incorporation of satellite cells in motor neurons of rock lobsters.

Previous electrophysiological experiments have shown that in the abdominal extensor muscles of rock lobsters, axons which were cut in surviving animals do not degenerate peripherally for several months, but conduct action potentials and release transmitter quanta on stimulation closely distal to the scar. Electron micrographs from the axon distal to the scar (in a reliably conducting region) show invasion of the axoplasmic space by nucleated cells, probably glia. After several months, the cell membranes of the invaders have vanished and apparently functional multiple nuclei remain. We suggest that decentralized axons may survive for months with the help of 'donated' nuclei.

Action Potentials↗
PubMed1989

Effect of Ca2+ diffusion on the time course of neurotransmitter release.

The three-dimensional (3D) diffusion model of Fogelson, A. L., and R. S. Zucker (1985. Biophys. J. 48: 1003-1017) has been employed as the basis of a refined version of the "Ca theory" for neurotransmitter release. As such, it has been studied here as to its ability to predict the time course of release under various conditions. In particular, conditions were chosen in which the temporal variations in intracellular Ca2+ concentration, the sole factor controlling the release according to the Ca theory, were modified and tested experimentally. The predictions of this model were compared with the experimental results. It is shown that the 3D diffusion model, similarly to earlier simpler versions of the Ca theory, predicts that the time course of release is highly sensitive to both the level of depolarization and the level of the resting concentration of intracellular Ca2+ Moreover, the 3D diffusion model predicts that the time course of release is insensitive to changes in temperature. In contrast, the experimental results show that the time course of release is invariant to the level of depolarization and to the resting level in intracellular Ca2+, but highly sensitive to variations in temperature.

Animals↗
PubMed1988

Long-term facilitation of synaptic transmission demonstrated with macro-patch recording at the crayfish neuromuscular junction.

Recordings of synaptic currents from the crayfish opener muscle were made with a macro-patch recording technique, permitting clear detection of neurotransmitter quanta at individual nerve terminals before and after induction of long-term facilitation (LTF). Depolarization of the terminal by propagated action potentials or by local intracellular pulses induced LTF. The quantal content was increased on average by 93%. Binomial analysis indicated increased probability of release and also increased number of available quantal units. The increase occurred regardless of a blockade of sodium, calcium or potassium channels by appropriate pharmacological agents. Presynaptic recording with an intracellular microelectrode showed no change in presynaptic electrical properties. Also, there were no changes in the synaptic delay. It is concluded that LTF results from a depolarization-dependent alteration of synaptic release sites.

Action Potentials↗
PubMed1988

The 'Ca-voltage' hypothesis for neurotransmitter release.

The 'Ca-voltage' hypothesis for neurotransmitter release was reinvestigated by studying the kinetics of neurotransmitter release. These were independent of changes in intracellular or extracellular Ca2+ concentration. It is concluded that initiation and termination of release do not result from rapid entry and removal of Ca2+ although Ca2+ is essential for release. Quantal release of transmitter requires depolarization-dependent transformation of a membrane molecule from an inactive form T to a Ca2+-binding form S. The depolarization-dependent T----S transformation initiates release in the presence of Ca2+. The S----T transformation upon repolarization stops release even though the Ca2+ concentration at release sites is still high.

Animals↗
PubMed1988

Presynaptic effects of d-tubocurarine on neurotransmitter release at the neuromuscular junction of the frog.

1. Presynaptic effects of d-tubocurarine on neurotransmitter release were examined at the frog neuromuscular junction, using intracellular and extracellular recording techniques. 2. d-Tubocurarine in concentrations of 10(-7)-10(-6) M decreased the quantal content (m) measured by the coefficient of variation and failure methods. 3. d-Tubocurarine produced a shift to the right of the curve relating log quantal content to log [Ca2+]o without changing the slope. 4. The duration of twin-impulse facilitation was not affected by 5 x 10(-7) M-d-tubocurarine. Early facilitation was higher in d-tubocurarine. 5. d-Tubocurarine altered the synaptic delay histogram. The peak of the histogram was shifted to longer delays. Prolongation of the minimal delay was seen in most but not all experiments. 6. These results suggest that d-tubocurarine inhibits release of neurotransmitter by affecting a stage in the process of release, which occurs after the entry of Ca2+ ions.

Animals↗
PubMed1987

Quantal currents evoked by graded intracellular depolarization of crayfish motor axon terminals.

1. Quantal transmitter release was examined at nerve terminals of the excitatory motor axon of the crayfish opener muscle. The magnitude of synaptic currents, recorded with macro-patch electrodes at a nerve terminal, served as a measure of quantal size. Transmitter release was initiated by pulses of depolarizing current applied intracellularly to the axonal terminals after application of tetrodotoxin. Quantal release was altered by a variety of methods and the resulting quantal output and quantal size were measured. 2. Amplitude distributions of quantal events were obtained during experimental manipulations which altered the rate of quantal release by up to 25-fold. These manipulations consisted of: varying pulse amplitude or pulse duration; facilitating the release by prolonged depolarization; and application of a potassium channel blocker, 4-aminopyridine. 3. The amplitude of quantal events is impervious to marked changes in presynaptic depolarization and is not affected by experimental procedures which promote accumulation of calcium ions in the terminals. The vesicular mechanism of release, in which transmitter substance is prepackaged in vesicles which individually undergo exocytosis at a release zone, could account for the observed results.

4-Aminopyridine↗
PubMed1987

Influence of depolarizing pulse duration on the time course of transmitter release in lobster.

1. Experiments have been made at lobster neuromuscular synapses to study synaptic delays and in particular the phenomenon known as 'latency shift'. Earlier work had suggested that synaptic delay becomes prolonged when pulses of long duration are applied to presynaptic terminals. 2. By observing single quanta, prolonged depolarizing pulses at low and moderate amplitudes have been shown to shift the peak of the synaptic delay histogram. There is however no increase in the minimal delay. 3. The apparent differences between these and earlier results have been shown to depend on differences in experimental procedures. In particular, in the present study equal numbers of pulses are applied at the various pulse durations and the number of quanta that had been released is presented.

Action Potentials↗
PubMed1987

Augmented synaptic release by one excitatory axon in regions in which a synergistic axon was removed in lobster muscle.

1. In the lobster, every fibre of the lateral abdominal extensor muscle is innervated by two excitatory axons. When one of the excitatory axons (the common excitor) was removed chronically by intracellular injection of pronase, terminals of the remaining axon (the specific L1 excitor) showed augmented transmitter release. 2. Evidence as to the mechanism of this strengthening can be obtained taking advantage of the peculiar innervation pattern of the abdominal extensors. The L1 excitor axon of one segment sends a branch to part of the next posterior segment. The common excitor axon innervates only muscle fibres of its own segment. 3. 10-20 days after removing the common excitor axon of segment II, the quantum content of release of terminals of the L1 excitor axon was measured in segments I, II and III. Terminals of the L1 excitor axon of segment I which innervate segment II released much more transmitter than controls, while the terminals of the same axon innervating segment I remained normal. Similarly, terminals of the L1 excitor axon of segment II became 'stronger' in segment II but remained normal in segment III. 4. It is concluded that only those terminals of one axon which innervate targets with reduced innervation increased the average release rate. It seems that the signal for synaptic strengthening, after removal of a synergistic axon, is generated and acts locally in partially denervated muscle fibres.

Action Potentials↗
PubMed1987

Latency of transmitter release at crayfish motor nerve endings examined by intracellular depolarization.

Latency of release of individual quanta of transmitter was studied at neuromuscular junctions of a crayfish (Procambarus clarkii). Postsynaptic quantal currents were recorded at individual motor nerve endings with a macropatch electrode while the subterminal axon branch was depolarized by current passed through an intracellular microelectrode. For depolarizing currents of moderate size, the latency of transmitter release did not change when the duration of the depolarizing current was altered. Previous studies in which a contrary result was obtained may have been compromised by artefacts or by the sampling methods employed. The present results do not support the hypothesis of a depolarization-induced "repressor" of quantal release.

Animals↗
PubMed1987

Strengthening of synaptic inputs after elimination of a single neurone innervating the same target.

The problem of 'competition' between neurones innervating the same target can be studied in simple neural systems such as the central nervous system of the leech and the lobster neuromuscular junction. Intracellular injection of pronase to kill selectively a single neurone shows that, in the leech, removal of one neurone is a sufficient signal to produce compensatory changes. After removal of a given neurone, only neurones of the same function respond to innervate the 'vacant territory'. This was shown both for a motor neurone (annulus erector) and sensory neurones (T or N). Thus the response is very specific. The lobster neuromuscular junction, with its multiple excitatory and inhibitory innervation, has advantages for the study of changes in synaptic efficacy of the remaining neurones after removal of a defined neurone releasing the same or a different transmitter. Killing the inhibitory neurone produced prolongation of the excitatory synaptic current because of a prolonged channel open time. When an excitatory axon is killed the remaining excitatory axon releases more transmitter. Over a period of 10 days, there is first a strengthening of existing synapses, then the appearance of new release sites and sprouting. Only those terminals of a neurone that innervate a territory with reduced innervation become stronger, while other terminals of the same axon remain normal. Cutting of axons produces different responses from those seen after killing single neurones.

Animals↗