PubMed Health⌕ Search

Biomedical subjects

R Rahamimoff

Publications and source records attributed to R Rahamimoff.

At least 55 records · Page 3Linked to original sources
PubMed1980

Regulation of acetylcholine liberation from presynaptic nerve terminals.

Acetylcholine is liberated from motor nerve terminals either as a molecular leakage or as quantal packages; the latter form of release is responsible for signaling across the neuromuscular synapse. Three main factors determine the number of quanta liberated by the nerve impulse: the degree of presynaptic depolarisation, the frequency of activation of the nerve terminal, and calcium ion concentration in the extracellular medium. These factors seem to act yb changing the free calcium ion concentration [Ca]in in the presynaptic nerve terminal. Thus, processes that change [Ca]in will determine efficiency of synaptic transmission. These processes include fluxes of calcium ions across the presynaptic membrane and reversible translocation by intracellular organelles such as mitochondria, vesicles and soluble molecules. The level of intracellular [Ca] can be changed by ion-containing liposomes. One of the main physiological determinants of the level of transmitter release is potentiation, where the increase in transmitter release is caused by transmembranal processes and intracellular translocation.

Acetylcholine↗
PubMed1980

Primary and secondary regulation of quantal transmitter release: calcium and sodium.

Calcium is the prime regulator of quantal acetylcholine liberation at the neuromuscular junction; its entry through the presynaptic membrane and the level of free [Ca]in most probably determine the number of transmitter quanta liberated by the nerve impulse. The level of free [Ca[in, in turn, is controlled by a number of subcellular elements: mitochondria, endoplasmic reticulum, vesicles, macromolecules and the surface membrane. The action potential induced calcium entry is not the only factor responsible for coupling nerve terminal depolarization with increased transmitter release; increased transmitter release occurs also in the virtual absence of calcium ions in the extracellular medium, when a reversed electrochemical gradient for calcium probably exists during action potential activity. Several lines of evidence suggest that the entry of sodium ions is responsible for this augmented transmitter release: the tetanic potentiation observed under reversed calcium gradient is blocked by tetrodotoxin; tetanic and post-tetanic potentiation are augmented and prolonged by ouabain; the amplitude of the extracellular nerve action potential is reduced with high-frequency stimulation, in parallel with increased spontaneous quantal release. In addition, sodium-filled egg-lecithin liposomes augment quantal liberation. The augmentory effect of sodium on transmitter release is probably due to an intracellular calcium translocation, since no preferred timing after the action potential is observed. Thus, the level of [Na]in in the presynaptic nerve terminal can control indirectly the efficiency of synaptic transmission.

Acetylcholine↗
PubMed1978

Intracellular and extracellular calcium ions in transmitter release at the neuromuscular synapse.

The theme of this presentation has been to show that the control of transmitter release at the neuromuscular synapse is achieved by extracellular and intracellular calcium. For the fast information transfer represented by the end-plate potential, the electrochemical gradient for calcium across the presynaptic membrane and the associated calcium conductance seem to play the primary role. For slower processes such as tetanic and posttetanic potentiation, the combined effect of both sources for calcium determine the amount of transmitter liberated.

Acetylcholine↗
PubMed1978

Changes in transmitter release induced by ion-containing liposomes.

The changes in quantal transmitter release induced by egg phosphatidylcholine liposomes with different internal ionic composition were examined at the frog neuromuscular junction by using conventional electrophysiological techniques. It was found that liposomes containing calcium or sodium ions increase both evoked and spontaneous transmitter release, while liposomes containing potassium do not. The results suggest that phosphatidylcholine liposomes are able to transfer their aqueous medium into the presynaptic nerve terminal.

Acetylcholine↗
PubMed1978

Quelling of spontaneous transmitter release by nerve impulses in low extracellular calcium solutions.

1. The effect of nerve stimulation on spontaneous transmitter release was studied at the frog neuromuscular synapse which was bathed in a solution containing very low extracellular calcium concentration. Conventional methods for intracellular and extracellular recording were used and the pattern of quantal liberation following the nerve stimulus was determined. 2. Stimulation of the motor nerve (at rates between 0.09 and 2Hz) caused a reduction in the frequency of the miniature e.p.p.s in comparison to the prestimulation values. 3. The mean distribution of the time of occurrence of the miniature e.p.p.s during the interstimulus period showed periodic oscillations. 4. The quelling effect of nerve stimulation on transmitter release is explained by the hypothesis that a low [Ca]o a reversed electrochemical gradient for calcium occurs and nerve stimulation causes an increased calcium conductance leading to calcium efflux which in turn temporarily reduces [Ca]i and transmitter release.

Action Potentials↗
PubMed1978

The role of calcium ions in tetanic and post-tetanic increase of miniature end-plate potential frequency.

1. The role of Ca ions in transmitter release changes, during and after high frequency stimulation of the motor nerve (10--100 Hz), was examined at the frog neuromuscular junction. 2. The stimulation-induced changes in miniature end-plate potential frequency (f) resembled the changes in end-plate potential amplitude recently described by Magleby and Zengel (1975, 1976). 3. The effects of tetanic stimulation on f under inward electrochemical gradient for Ca ions were compared with those under reversed gradient and four differences were found: (a) The increase in f during the tetanus under reversed Ca gradient conditions is much smaller than with an inward Ca gradient. (b) The increase in f under reversed Ca gradient is preceded by a small decrease in f, whereas with an inward Ca gradient an immediate increase in f is observed. (c) After the termination of the tetanus with a reversed Ca gradient, there is a further increase in f, compared to a decrease with an inward Ca gradient. (d) The augmentation phase of post-tetanic potentiation was practically abolished. 4. The experimental results are explained by assuming that high frequency nerve stimulation causes an increase in transmitter release by at least two distinct processes: influx of Ca ions through the presynaptic membrane and release of Ca ions from intracellular stores. It is suggested that Na ions couple nerve activity to intracellular release of Ca.

Action Potentials↗
PubMed1978

Clumping and oscillations in evoked transmitter release at the frog neuromuscular junction.

1. Time series analysis of evoked transmitter release was performed at the frog neuromuscular synapse. 2. Clumping of end-plate potentials with similar amplitude was found in the time domain. 3. At low quantal contents periodic oscillations were observed with a period of 14 sec. 4. Clumping and oscillations are phenomena of presynaptic origin. 5. The results are explained on the hypothesis that periodic fluctuations occur in Ca concentration inside the presynaptic nerve terminal.

Animals↗
PubMed1977

Is hyperosmotic neurosecretion from motor nerve endings a calcium-dependent process?

Spontaneous liberation of neurotransmitter quanta is strongly affected by the osmotic pressure of the extracellular fluid. Elevation of the osmolarity by 20-30% increases the rate of release from motor nerve endings by more than one order of magnitude. In this respect the neuromuscular junction resembles some other secretory systems. The mechanism of this hyperosmotic neurosecretion is not yet understood; extracellular calcium ions are not directly responsible, since this effect can be produced in their absence. Recently, it has been suggested that the liberation of neurotransmitter is regulated by the intracellular concentration of free calcium ions. We have therefore examined the hypothesis that hyperosmotic neurosecretion originates from an increase in internal calcium concentration ([Ca]in). At the frog neuromuscular synapse however, it is impossible at present to estimate directly free [Ca]in; hence we used an indirect technique, which is based on two assumptions; first, the frequency of the miniature endplate potentials (m.e.p.p.s.) reflects free [Ca]in. Second, the movement of calcium ions across the presynaptic membrane is governed by the electrochemical gradient, and by the calcium conductance (g(Ca)). If hyperosmotic neurosecretion is caused by an increase in [Ca]in, then increasing g(Ca), under reversed electrochemical gradient for the calcium should cause a reduction in the effect of hyperosmotic stress on transmitter release. We report that hyperosmotic neurosecretion is dependent on [Ca]in.

Animals↗
PubMed1975

On the role of mitochondria in transmitter release from motor nerve terminals.

1. The changes in transmitter release produced by mitochondrial inhibitors has been studied at the frog neuromuscular junction using conventional electrophysiological techniques for stimulation and intracellular recording. 2. Inhibitors of the electron transport chain and inhibitors of oxidative phosphorylation produce an increase in the frequency of appearance of the miniature end-plate potentials. This increase in frequency is observed also in calcium-free media. Mitochondrial inhibitors also augment the amount of transmitter liberated by a nerve impulse. 3. Ruthenium red, which is an inhibitor of calcium uptake by mitochondria, increases the spontaneous transmitter release but decreases the quantal content. The latter effect of Ruthenium red is antagonized by calcium. 4. The mitochondrial content of the motor nerve terminals is, on the average, 6.59%. 5. The experimental results are explained on the hypothesis that spontaneous release of transmitter reflects the resting level of intracellular free calcium and the evoked release reflects the sum of the resting calcium and the calcium brought in by the action potential. The mitochondria play a role in transmitter release by participating in the regulation of the intracellular free Ca.

Action Potentials↗
PubMed1975

Tonic release of transmitter at the neuromuscular junction of the crab.

1. Synaptic transmission was studied at the neuromuscular junction of the crab Ocypoda cursor, using conventional electrophysiological technique. 2. It was found that fibres of the extensor muscle and those composing the internal layer of the closer muscle have only post-synaptic inhibition (S fibres) while the fibres at the external layer of the closer muscle have in addition presynaptic inhibition (R fibres). 3. In S fibres, addition of GABA reduces input membrane resistance (Rm) and e.p.s.p. amplitude approximately to the same degree. The effect shows desensitization. In R type fibres, GABA reduces the e.p.s.p. much more than expected from changes in Rm. The post-synaptic effect of GABA on Rm shows desensitization, while the presynaptic effect does not show desensitization. 4. In about 50 percent of the cases, after desensitization occurred, Rm increased by about 10-30 percent above the control. Similar increase in Rm occurred after application of picrotoxin. These results suggest that initially the membrane resistance was lower due to tonic release of inhibitory transmitter. 5. The Q10 of Rm was found to vary between 2 and 3. In Ca2+ free media, Cl- free media, or in picrotoxin the Q10 is about 1-3. 6. In R fibres, addition of picrotoxin increased the amplitude of the e.p.s.p. by 30-60 percent above the expected increase due to changes in Rm. 7. In S fibres the mean slope of log e.p.s.p. vs. log [Ca2+] was found to be 1-63, while in R fibres the slope was 0-93. These results suggest the presence of tonic release of the inhibitory transmitter which acts both post-synaptically and presynaptically.

Animals↗
PubMed1974

A note on the interaction of spontaneous and evoked release at the frog neuromuscular junction.

1. The interaction between spontaneous miniature end-plate potentials and evoked end-plate potentials was investigated at the frog neuromuscular junction using focal extracellular recording techniques.2. End-plate potentials evoked immediately after a spontaneous miniature potential were facilitated by up to 20%. The percentage facilitation was negatively correlated with the average quantal content of the end-plate potential.

Animals↗