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H Parnas

Publications and source records attributed to H Parnas.

At least 91 records · Page 5Linked to original sources
PubMed1983

A case study of linear versus non-linear modelling.

Theories for the facilitation of neurotransmitter release are discussed in a case study of the properties of linear and non-linear models for a phenomenon whose time course can be represented by a sum of decaying exponentials. Particular attention is paid to the effects of a "key factor" on the slopes and amplitudes of the exponentials that can be derived from semilog plots of the data. It is shown that the presence of such effects can give strong evidence for the inappropriateness of linear models. A non-linear model is demonstrated to be capable of describing the changes with extracellular Ca concentration of straight line segments that fit data in semilog plots of facilitation as a function of time. The conclusion is reached that even if data seems to be representable by several independently alterable exponentials one must be cautious in drawing inferences concerning the number, linearity, or independence of the underlying processes.

Action Potentials↗
PubMed1983

Neurotransmitter release and its facilitation in crayfish muscle. VI. Release determined by both, intracellular calcium concentration and depolarization of the nerve terminal.

In excitatory neuromuscular junctions of crayfish quantal synaptic currents were recorded focally by means of a macro-patch-clamp electrode. Through the same electrode the nerve terminal was depolarized by current pulses which elicited quantal postsynaptic currents (pEPSCs). The terminals were electrically inexcitable and the quantum content (m) of pEPSCs increased gradually to a saturation level with rising pulse amplitude. A test-pEPSC was elicited by constant current pulses, and its facilitation (Fc) by a preceding pEPSC of varying amplitude was studied. Amplitude and duration of Fc are measures of the amount of Ca entry during the prepulse. These values had a maximum consistently at a much lower prepulse amplitude than necessary to reach maximum release during the prepulse. The potential dependence of Fc is as expected for a potential dependent Ca-entry into the terminal. The fact that release during the prepulse rose for large depolarizations while Fc and thus Ca-entry decreased, indicates a direct promotion of release by depolarization. In another type of experiment the Ca concentration in the terminal ([Ca]i) was increased greatly by series of depolarizations. During a following test-pEPSC thus [Ca]i was at an approximately constant high level. However, variations of the amplitude of the test depolarization pulse caused changes of the test-pEPSC by several orders of magnitude, which must be attributed to a direct control of quantal release by depolarization. The mechanism of this direct effect of membrane potential is discussed, extending our model of synaptic release which only contained control by [Ca]i. The decisive role of control of release by membrane potential for the termination of release after Ca entry is emphasized.

Action Potentials↗
PubMed1982

Neurotransmitter release and its facilitation in crayfish muscle. V. Basis for synapse differentiation of the fast and slow type in one axon.

Excitatory postsynaptic currents (EPSCs) were recorded extracellularly from synaptic spots on crayfish opener muscle fibers. Synapses on the proximal fiber bundle were characterized as fast, with a relatively high quantal-release rate m of 0.2-5 and a low twin-pulse facilitation Fs of 1.1-3, at 13.5 mM [Ca]o and low (0.5/s) repetition rate. Under the same conditions, distal "slow" synapses had a release rate m of 0.02-0.4 and a facilitation Fs of 2-4. When the [Ca]o was varied between 1.7 and 27 mM, release and facilitation were much less affected in proximal, fast synapses than in distal, slow ones. The average maximal slope of the log release to log [Ca]o relation was 1.5 in proximal, and 3.1 in distal synapses, while the average maximal facilitation Fs was 2.5 in proximal and 4.7 in distal synapses, respectively. Assuming saturation kinetics for entry of Ca into the terminal and release of transmitter, possible variations of parameters generating the fast-slow differentiation were explored. Excluding a number of possibilities, it was found that in addition to a higher maximal release level, fast synapses seem to have a higher resting [Ca]i and/or a lower cooperativity of the release mechanism, as compared to slow synapses.

Animals↗
PubMed1982

Neurotransmitter release and its facilitation in crayfish. I. Saturation kinetics of release, and of entry and removal of calcium.

Release and facilitated release of transmitter at neuromuscular junctions of the crayfish Astacus were measured as a function of [Ca]0 at single junctions using a patch clamp technique. Tests were made of a quantitative model that relates release of transmitter to [Ca]i. The model assumes three processes, entry of Ca during the action potential, release of transmitter as a function of [Ca]i, and removal of Ca after the action potential. Each process is described alternatively by linear kinetics or saturation kinetics, and predictions for different combinations of the equations are given. The main findings were in agreement with those predicted by the "saturation" model. The amplitude of synaptic current varies non-linearly with [Ca]0, log-log plot yielding a slope of about 1.6. The degree of facilitation at long intervals is an increasing function of [Ca]0. In addition, the duration of facilitation is prolonged as [Ca]0 is increased, to saturate at [Ca]0 of 9 mM.

Animals↗
PubMed1982

Neurotransmitter release and its facilitation in crayfish. II. Duration of facilitation and removal processes of calcium from the terminal.

Excitatory postsynaptic currents (EPSCs) were recorded extracellularly from synaptic spots on crayfish opener muscles. Facilitation was measured in twin pulses with different intervals. When the extracellular calcium concentration, [Ca]0, was raised from 1.7 to 13.5 mM, the duration of facilitation was increased more steeply than can be explained by the higher entry of Ca. The discrepancy can be accounted for by assuming two saturable Ca removal processes, one being inhibited at high [Ca]0. If [Na]0 was reduced to 50 or 25%, facilitation at low [Ca]0 (e.g. 3.4 mM) was greatly prolonged, while at high [Ca]0 (13.5 mM) no effect was observed. It is concluded that one of the Ca removal processes, R1, depends on [Na]0 and is inhibited by [Ca]0; probably it is a Cai in equilibrium with Na0 exchange. R1 is predominant at low [Ca]0 and is largely responsible for the short duration of facilitation there. Other removal processes, R2, are not affected appreciably by [Ca]0 and [Na]0, and they predominate at high [Ca]0. Approximate values for the kinetic constants of R1 and R2 and the inhibition of R1 were estimated.

Animals↗
PubMed1982

Neurotransmitter release and its facilitation in crayfish. III. Amplitude of facilitation and inhibition of entry of calcium into the terminal by magnesium.

Excitatory postsynaptic currents (EPSCs) were recorded extracellularly from synaptic spots on crayfish opener muscles. Release of transmitter was determined by counting the average number of quanta which appear after a stimulus. When [Mg]0 was increased from 2.5 to 12.5 mM, release was inhibited. Quantitatively the effect of [Mg]0 could be described by a competitive inhibition of the entry (not of the release) of Ca2+ after an impulse, with apparent dissociation constants KMg between 1.4 and 18 mM [Mg]0, assuming saturation kinetics for entry of Ca2+ and release. At constant [Ca]0, twin pulse facilitation (Fs) for short intervals (about 10 ms) increased when [Mg]0 was raised from low values, reached a maximum at a certain [Mg]0(F) and unexpectedly decreased again at higher [Mg]0. At higher [Ca]0, [Mg]0(F) shifted to higher values. This maximum of facilitation is predicted qualitatively by our theoretical model. However, the amplitude of facilitation was larger than predicted theoretically, and the [Mg]0(F) were smaller than predicted. The theoretical possibilities to correct these discrepancies within the framework of 'residual calcium' based facilitation and saturation kinetics of entry and release were analyzed, but all were in conflict with experimental findings. It is concluded that an essential element is missing in the present theory of facilitation.

Animals↗
PubMed1982

Neurotransmitter release and its facilitation in crayfish. IV. The effect of Mg2+ ions on the duration of facilitation.

Excitatory synaptic currents (EPSCs) were recorded extracelularlly from synaptic spots on crayfish opener muscles. The decay of facilitation after a first pulse was measured by a second pulse given at increasing intervals; the duration of facilitation TF was the interval after which the second EPSC had 1.1 times the amplitude of the first one. Increasing [Mg]0 in the range from 0.5-12.5 mM at low [Ca]0 (1.7-4.5 mM) led to a monotonic prolongation of facilitation. TF showed a S-shaped dependence on [Mg]0, rising very steeply at 2-5 mM [Mg]0. At higher [Ca]0, and also at half normal [Na]0, an increase of [Mg]0 did not affect the decay of facilitation appreciably. As shown before, the decay of facilitation is due to two Cai-removal processes, R1 and R2. Mg0 inhibits only the R1 process, which is also inhibited by high [Ca]0, is dependent on normal [Na]0 and has the characteristics of a Cai in equilibrium with Na0 exchange. As one possible mechanism, competition of Mg0 with Na0 at the extracellular loading site of the exchange is discussed quantitatively.

Animals↗
PubMed1981

The effect of magnesium on the time course of facilitation at the crayfish neuromuscular junction.

Synaptic currents (EPSCs) were recorded extracellularly from single junctions. Pairs of EPSCs were elicited at different intervals, the increase of amplitude of the second one facilitation. Elevated Mg concentrations reduced the amplitude of the EPSC and prolonged facilitation. Also, if the amplitude of the EPSCs at high Mg is made the same as in the control, by raising [Ca]0, facilitation is still prolonged. It is concluded that Mg inhibits not only the entry of Ca into the nerve terminal but also its removal.

Animals↗
PubMed1977

Computer evidence concerning the chemotactic signal in Dictyostelium discoideum.

Observed pulsatile aggregation of cellular slime mould amoebae is simulated on a computer. One spatial dimension is considered. In the simulation, attractant is rapidly secreted by the cells, after a delay period, when a superthreshold attractant concentration is sensed. Cells are refractory to further signals after secretion. Once secreted, the attractant diffuses and is hydrolysed. Movement results if a cell's extending pseudopods sense a supercritical increase of attractant; if increases are sensed on both sides, a sufficiently large difference can also initiate movement. The movement continues for a period independently of further signals, but then can be reversed by a attractant increase (at the back of the cell) that surpasses a high threshold. After 100s, motion stops and the threshold for movement reverts to normal. With the above rules, and with parameter values taken, as far as possible, from the literature, the simulation provides the observed pattern of aggration. Outward moving waves of attractant and organized inward pulsatile 'steps' of cell movement surround a cell that sevretes autonomously every few minutes. Other rules fail to give this picture, or give it only for a relatively narrow range of parameter values. It appears that of the various possible signals for chemotaxos, the most likely to be used by the amoebae is a temporal increase of attractant as sensed by extending pseudopods. Nonetheless, we connot rule out the 'classical' hypothesis that cells directly sense concentration differences.

Cell Aggregation↗
PubMed1976

Theoretical analysis of parameters leading to frequency modulation along an inhomogeneous axon.

1. Theoretical computations were conducted on a computer model of a segmented, nonhomogeneous axon to understand the mechanism of frequency block of conduction. 2. The model is based on the Hodgkin-Huxley equations modified in several ways to better describe the cockroach axon. We used cockroach parameters where available. 3. The increase in fiber radius was spread over a series of segments to approximate a taper. We found that a taper allows a larger overall increase in fiber diameter than a single step to be successfully passed. 4. We studied effects on a train of impulses. The modified equations included effects due to changes in extracellular potassium concentration resulting from the repetitive firing of the axon. 5. An increase in diameter which allows a single spike to pass blocks the subsequent impulses in a train at the taper if potassium concentration variability is introduced. This could explain the low-pass filter characteristics of axon constrictions. 6. Results of the model fit well with the experiemental spike shape and height. Data were computed for the refractory period and its dependence on the taper parameters.

Action Potentials↗