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Biomedical subjects

I Parnas

Publications and source records attributed to I Parnas.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1983

Synaptic integration mechanisms. Theoretical and experimental investigation of temporal postsynaptic interactions between excitatory and inhibitory inputs.

The effect of temporal activation of two closely adjacent synaptic inputs upon the postsynaptic output (voltage amplitude and time integral) is analyzed theoretically and experimentally. It is shown that (a) under certain conditions, maximal nonlinearity in the summation of postsynaptic potentials is obtained with asynchronous activation of the two synaptic inputs rather than with simultaneous activation; (b) the time integral of the voltage is more sensitive to the timing of the synaptic inputs than is the voltage amplitude; (c) an input, which by the classical definition is inhibitory, under defined conditions can and does increase the amplitude (and area) of an excitatory synaptic potential, and thus acts as an excitatory input.

Animals↗
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↗
PubMed1982

Physiological responses, receptive fields and terminal arborizations of nociceptive cells in the leech.

The physiological responses, receptive fields and morphology of individual nociceptor (N) neurones have been studied in the leech. In each of the midbody ganglia there are four N cells (two on either side). Each N cell has a distinctive territory that it supplies in the periphery, on the surface or internally. 1. Both N cells respond selectively to noxious mechanical stimuli applied to the skin but not to touch, light, pressure or stretch. The receptive field of each cell is well defined and covers roughly the same area, extending from the dorsal midline to the ventral midline, with considerable overlap. 2. One of the N cells, situated more medially in the ganglion, also fires at high frequencies in response to mechanical stimulation, such as pinching or squeezing, of the connective tissue lining the viscera. In contrast, the other N cell (situated laterally in the ganglion) is activated by pressure or pinches applied to the opening of the excretory duct but not the gut. 3. Following injection of horseradish peroxidase into the soma, axons of N cells appear as unspecialized fine processes about 1 micrometer in diameter, in the dermis of the leech, deep to the layer of epidermal cells. In addition, at specific sites in the skin, the N cell situated laterally in the ganglion makes distinctive coiled terminals in association with the expanded dendrites of large neurones in the periphery, the functions of which are unknown. This finding raises the possibility that lateral N cells may perform some additional role as yet not understood.

Action Potentials↗
PubMed1982

Expanded receptive fields of cutaneous mechanoreceptor cells after single neurone deletion in leech central nervous system.

1. Individual sensory neurones responding to touch (T) and to noxious (N) stimuli applied to the skin of the leech were killed by injecting pronase into their cell bodies, situated within the C.N.S. This procedure destroys one neurone in its entirety without damaging the cells. 2. When three out of four N cells within a ganglion have been killed, the receptive field of the remaining N sensory cell expands to cover the denervated area of skin. Similarly the field of the touch cell that innervates dorsal skin spreads across the mid line to innervate contralateral skin after the three touch cells on that side have been deleted. 3. The spread is graded and develops with time. The earliest effects appear within 4 weeks and the full spread develops by 3 months. 4. No detectable spread of receptive fields occurs if only two N cells, one on each side, are killed. 5. Following deletion of N cells, the receptive fields of T and pressure sensory cells are unaffected. Similarly, if T cells have been killed, the fields of N cells or pressure cells do not become enlarged. 6. These results represent a modality-specific mechanism by which one sensory cell can be influenced to extend the territory it supplies in the periphery in response to a minimal lesion without its own terminals having been damaged.

Action Potentials↗
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↗
PubMed1981

Membrane conductance and action potential of a regenerating axonal tip.

The electrical membrane properties of axotomized and regenerating giant axons from the nerve cord of the cockroach Periplaneta americana were studied. Immediately after axotomy there was a decrease in resting potential, input resistance, and action potential amplitude near the cut end. This decrease was followed by the disappearance of the sodium-dependent action potential; an increase in the resting membrane conductance to K+, Na+, and Ca2+; and the appearance of a calcium-dependent action potential.

Action Potentials↗
PubMed1980

Mechanism of long-lasting synaptic inhibition in Aplysia neuron R15.

1. Long-lasting inhibition is a synaptically mediated response found in certain molluscan nerve cells that fire action potentials in bursts. It is elicited by repetitive stimulation of a presynaptic nerve and may last for minutes or hours after stimulation. 2. Voltage-clamp techniques were employed to measure the voltage dependence of the synaptically elicited current. Current-voltage curves were obtained by stepping or sweeping the voltage over the range -40 to -120 mV. 3. Long-lasting inhibition was found to be mediated by two separate conductance mechanisms. A component that reverses near -80 mV is most prominent at times up to 5 min following stimulation. A component with no reversal potential between -40 and -120 mV predominates at later times. 4. The reversible component is attenuated by reducing the intensity of stimulation of the presynaptic nerve, by injection of TEA into the postsynaptic cell, or by activation of a potassium conductance with serotonin prior to stimulation of the nerve. Thus, the reversible component appears to be mediated by an increase in potassium conductance. 5. The effects of the nonreversible component measured in the soma appear to be too large to attribute it to a conductance change that is electrically "distant" from the soma. It is attenuated by turning off a resting inward ion conductance with dopamine prior to stimulation of the nerve. It is not affected by short exposure to ouabain, but is attenuated by longer exposures that reduce the sodium and calcium gradients. Thus, the nonreversible component may be mediated by a decrease in voltage-dependent inward current flow carried by sodium or calcium.

Action Potentials↗
PubMed1979

Differential conduction block in branches of a bifurcating axon.

1. Propagation of action potentials at high frequency was studied in a branching axon of the lobster by means of simultaneous intracellular recording both before and after the branch point. 2. Although the branching axon studied has a geometrical ratio close to one (perfect impedance matching) conduction across the branch point failed at stimulation frequencies above 30 Hz. 3. The block of conduction after high frequency stimulation occurred at the branch point per se. The parent axon and daughter branches continued to conduct action potentials. 4. Conduction block after high frequency stimulation appeared first in the thicker daughter branch and only later in the thin branch. 5. With high frequency stimulation there was a 10-15% reduction in amplitude of the action potential in the parent axon, a corresponding decrease in the rate of rise of the action potential, a 25-30% decrease in conduction velocity, marked increase in threshold and prolongation of the refractory period. In addition the membrane was depolarized by 1-3 mV. 6. Measurements of the membrane current using the patch clamp technique showed a large decrease in the phase of inward current associated with the action potential, before the branching point. 7. The small membrane depolarization seen after high frequency stimulation is not the sole cause of the conduction block. Imposed prolonged membrane depolarization (8 mV for 120 sec) was insufficient to produce conduction block. 8. In vivo chronic extracellular recordings from the main nerve bundle (which contains the parent axon) and the large daughter branch revealed that: (a) the duration and frequency of trains of action potentials along the axons exceeded those used in the isolated nerve experiments and (b) conduction failure in the large daughter branch could be induced in the whole animal by electrical stimulation of the main branch as in the isolated preparation. 9. Possible mechanisms underlying block of conduction after high frequency stimulation in a branching axon are discussed.

Action Potentials↗
PubMed1979

Mechanisms involved in differential conduction of potentials at high frequency in a branching axon.

1. The ionic mechanisms involved in block of conduction of action potentials following high frequency stimulation were studied in a branching axon of the lobster Panulirus penicillatus. 2. A 2-3 mM increase in extracellular K concentration (normal concentration 12 mM) produced block of conduction into both daughter branches. 3. While conduction block induced by high frequency stimulation occurs first into the large daughter branch and only later into the smaller one, propagation into both branches is blocked simultaneously by increased extracellular K concentration. 4. Increasing extracellular K by 2-3 mM resulted in membrane depolarization, reduction in membrane resistance and reduced excitability. The latter two effects were larger than expected from the small depolarization. It appears that increase of extracellular K has direct effects on membrane excitability. 5. It is suggested that block of conduction after high frequency stimulation results from accumulation of K in the extracellular space. However, in order to account for differential conduction block in the two branches one must assume differential buildup of extracellular K concentration around the two branches during high frequency stimulation. 6. Ultrastructural studies using La and horseradish peroxidase as extracellular markers show that the space around the two branches is similar and is open to the extracellular space. Therefore differences in periaxonal volume cannot account for differential buildup of K around the two branches. 7. It is demonstrated that the lobster axon has a Na+/K+ electrogenic pump. After blocking this pump with ouabain, stimulation at high frequency resulted in a conduction block in the two branches almost at the same time. 8. Injection of Ca2+ intracellularly into the thick branch prevents or delays the appearance of conduction block after high frequency stimulation. 9. A mechanism based on these findings is suggested to explain the differential conduction block seen after high frequency stimulation in a branching axon with almost ideal impedance matching.

Action Potentials↗
PubMed1979

A mathematical model for conduction of action potentials along bifurcating axons.

1. A mathematical model based on the Hodgkin-Huxley equations is derived to describe quantitatively the propagation of action potentials in a branching axon. 2. The model treats the case of a bifurcating axon with branches of different diameters. The solution takes into account the changes in space constant in the different regions. 3. The model allows for investigating parameters leading to preferential conduction of action potentials in one daughter branch as seen experimentally. 4. Assuming that the only difference between the various daughter branches is in their diameters, conduction blocks should occur simultaneously rather than differentially into all daughter branches when the geometrical ratio is greater than 10. 5. In order to obtain differential conduction into the two branches changes in ionic concentrations due to the repetitive action potentials had to be introduced into the equations. 6. We find that conditions which allow differential buildup of K concentration around the two branches, produce differential conduction block. These conditions may be different periaxonal spaces around the branches or different time constant for recovery processes that eliminate K from the periaxonal space. 7. The effects of an inexcitable branch on conduction of action potentials in the second branch are described. 8. We find that the membrane current which is associated with the action potential is much more sensitive than the action potential itself and shows more distinct changes near regions of inhomogeneity such as a branch point, a step increase in diameter or an inexcitable branch.

Action Potentials↗