Search PubMed⌕ Search

Biomedical subjects

R Miledi

Publications and source records attributed to R Miledi.

At least 289 records · Page 16Linked to original sources
PubMed1972

The statistical nature of the acetycholine potential and its molecular components.

1. When a steady dose of acetylcholine (ACh) is applied to an end-plate, the resulting depolarization is accompanied by a significant increase in voltage noise.2. The characteristic properties of this ACh noise (amplitude and time course) are examined under various experimental conditions. The voltage noise is analysed on the assumption that it arises from statistical fluctuations in reaction rate, and in the frequency of the elementary current pulses (;shot effects') produced by the action of ACh molecules.3. The elementary ACh current pulse (amplitude approximately 10(-11) A), arises from a conductance change of the order of 10(-10) Omega(-1) which lasts for approximately 1 ms (at 20 degrees C), and produces a minute depolarization, of the order of 0.3 muV. It is associated with a net charge transfer of nearly 10(-14) C, equivalent to approximately 5 x 10(4) univalent ions.4. At low temperature, and during chronic denervation, the duration of the elementary current pulse increases, and the elementary voltage change becomes correspondingly larger.5. Curare has little or no effect on the characteristics of the elementary event.6. A comparative study of ACh and carbachol actions shows that carbachol produces considerably briefer, and therefore less effective, current pulses than ACh.

Acetylcholine↗
PubMed1972

Synaptic potentials in nerve cells of the stellate ganglion of the squid.

1. Intracellular recordings were made from nerve cells in the stellate ganglion of the squid.2. Stimulation of the preganglionic nerve evoked excitatory or inhibitory synaptic potentials, or a combination of both. Antidromic stimulation of the stellar nerves also evoked excitatory and inhibitory potentials in the cells. With both types of stimulation the synaptic potentials were built up of contributions from several axons indicating considerable convergence of excitatory and inhibitory inputs on the cells.3. Inhibitory, as well as excitatory, miniature synaptic potentials were recorded from the cells even after impulse activity had been blocked by tetrodotoxin.4. Glutamate applied iontophoretically to some cells produced a depolarization of their membranes. In other cases glutamate evoked a hyperpolarizing potential. Application of glutamate caused a decrease in the amplitude of excitatory synaptic potentials.

Action Potentials↗
PubMed1971

Tetanic and post-tetanic rise in frequency of miniature end-plate potentials in low-calcium solutions.

1. Miniature end-plate potentials (min.e.p.p.s) were recorded intracellularly from frog neuromuscular junctions.2. The ;phasic' release of transmitter which is directly related to nerve impulses was suppressed by withdrawal of Ca from the external medium plus addition of Mg.3. Under these conditions, min.e.p.p.s continued to be discharged even when EGTA was added, although in this case min.e.p.p. frequency appeared to decrease to about half the rate in normal Ringer.4. Tetanic stimulation of the nerve approximately doubled the rate of min.e.p.p.s even in Ca-free solutions with EGTA added.5. The tetanic increase in frequency was greater without EGTA and greater still with some Ca added. Therefore, it is concluded that the tetanic rise in min.e.p.p. frequency can occur even in the absence of the immediate ;phasic' release of transmitter normally induced by nerve impulses; and that the magnitude of the increase is related to Ca concentration.A possible relation between ;phasic' and ;residual' effects of nerve impulses is described.

Animals↗
PubMed1971

The effect of prolonged depolarization on synaptic transfer in the stellate ganglion of the squid.

1. Depolarization of the giant axon terminal of the squid causes local calcium influx which gives rise to transmitter release and post-synaptic response, and which under certain experimental conditions leads to a regenerative action potential in the presynaptic terminal itself.2. There has been conflicting evidence in the literature on the question whether the calcium permeability change in the terminal is rapidly inactivated, or whether it can persist with little diminution for hundreds of milliseconds during a depolarizing voltage step.3. Results are presented which show that there is little ;calcium inactivation', even when very large depolarizing steps are imposed on the terminal and maintained for periods of 1-2 sec.4. Contrary indications are examined and found to be attributable to an increase of potassium conductance, rather than direct inactivation of calcium conductance.

Action Potentials↗
PubMed1971

The effect of type D botulinum toxin on frog neuromuscular junctions.

1. Botulinum toxin type D blocks neuromuscular transmission in frogs. Motor nerve impulses continue to invade the nerve terminals but cease to evoke the phasic release of transmitter normally associated with them.2. Sensory receptors in the muscle continue to generate impulses even after 4 days of continuous exposure to botulinum toxin.3. Contrary to expectations, spontaneous miniature end-plate potentials did not disappear completely after botulinum intoxication; they still occurred, although with reduced frequency, in most end-plates. These miniature potentials had a skew amplitude distribution instead of the bell-shaped distribution of normal end-plates.4. The electron-microscopic appearance of botulinum-poisoned end-plates was not obviously altered.5. Even though after botulinum nerve impulses fail to release transmitter, tetanic nerve stimulation causes an increase in the frequency of miniature end-plate potentials. Many of the unit potentials which appear during the tetanic period are of an amplitude which is larger than that of spontaneous potentials, indicating that a different class of unit is being released preferentially. Some implications of this finding are briefly discussed.

Action Potentials↗
PubMed1971

Induction of the action potential mechanism in slow muscle fibres of the frog.

1. The electrical and structural characteristics of ;slow' muscle fibres of the frog were studied in normal and denervated muscles, and in muscles undergoing re-innervation by a mixed nerve containing large and small motor axons.2. In agreement with previous studies, slow fibres in normally innervated muscles were incapable of producing action potentials.3. Approximately 2 weeks after the sciatic nerve was transected or crushed, slow muscle fibres acquired the ability to generate action potentials. These fibres were positively identified as belonging to the slow type, because their passive-electrical and ultrastructural characteristics remained essentially unchanged after the operations.4. The action potential mechanism induced in slow fibres is sodium-dependent, and is blocked by tetrodotoxin.5. After long-term re-innervation by a mixed nerve, slow fibres lose their acquired ability to generate action potentials, presumably because small motor axons re-establish connexion with the fibres.6. It is concluded that the action potential mechanism of slow muscle fibres is under neural control, and is normally suppressed by small motor axons.

Action Potentials↗
PubMed1970

On the degeneration of rat neuromuscular junctions after nerve section.

1. A study was made of functional and structural changes during degeneration of end-plates in the rat diaphragm after phrenic nerve section at two levels.2. For 8-10 hr after cutting the nerve in the neck, all end-plates retain the ability to transmit impulses. During the following 8-10 hr, an increasing number of end-plates lose this ability so that after a total of about 20 hr, no end-plates can transmit.3. Transmission failure occurs abruptly at most end-plates. This failure is usually accompanied by cessation of spontaneous miniature end-plate potentials (min.e.p.p.s), though in a few cases min.e.p.p.s persist after junctional transmission has failed. Several degenerating junctions were observed where the frequency of min.e.p.p.s was very low, suggesting an intermediate stage in min.e.p.p. failure.4. The time of junctional failure depends on the length of the degenerating nerve stump. For each additional centimetre of nerve, failure is delayed about 45 min.5. Changes in ultrastructure of nerve endings closely parallel those of function. For about 8-12 hr after cutting the nerve, nearly all end-plates appear normal. During the period when transmission is failing, some end-plates are clearly undergoing structural break-down. By the time functional failure is complete, all end-plates appear grossly abnormal.6. During degeneration, the contents of the axoplasm undergo disruption and the nerve terminal breaks up into small fragments. In contrast, the Schwann cell appears to become very active and its processes extend into the synaptic cleft to surround fragments of the nerve terminal. Ultimately, the Schwann cell completely replaces the axon at the end-plate.7. Increasing the length of the peripheral nerve stump delays the onset of structural break-down. Disruption of end-plates near the site of nerve entry into the muscle occurs before those farther away.8. It is suggested that end-plate degeneration is triggered by a signal which passes from the site of injury to the nerve terminal. The duration of the period after transection when end-plates appear to be normal would then reflect the time required for this signal to travel the length of the isolated nerve stump.

Animals↗
PubMed1970

Further study of the role of calcium in synaptic transmission.

1. The effect of calcium on synaptic transmission has been studied by intracellular recording of pre- and post-synaptic potential changes in the stellate ganglion of the squid.2. For a given presynaptic ;input' (propagated spike, or local depolarizing pulse after tetrodotoxin treatment), the post-synaptic response increases with external calcium concentration [Ca](o) in a highly non-linear fashion, indicating that transmitter output varies with more than the second power of [Ca](o) over a certain concentration range.

Action Potentials↗
PubMed1970

Miniature potentials in denervated slow muscle fibres of the frog.

1. Pyriformis and iliofibularis muscles of the frog were studied with micro-electrodes. Both muscles contain a mixture of fast and slow muscle fibres, which can be distinguished by differences in their miniature end-plate potentials (min.e.p.p.s).2. In addition, the membrane time constant of fast fibres is < 20 msec, while that of slow fibres is > 200 msec.3. The characteristic difference in time constant persisted after denervation and allowed the identification of fibre type.4. Denervated slow fibres had min.e.p.p.s of variable time courses and skew amplitude distributions. Their frequency was lower than in normally innervated fibres, and could be increased by hypotonic solutions.5. In analogy with similar observations made previously in fast muscle fibres, it is suggested that after nerve degeneration the Schwann cells of small motor nerve fibres release packages of transmitter which give rise to min.e.p.p.s.

Acetylcholine↗