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Biomedical subjects

R Miledi

Publications and source records attributed to R Miledi.

At least 307 records · Page 17Linked to original sources
PubMed1969

Strontium and quantal release of transmitter at the neuromuscular junction.

1. Previous work has shown that in calcium-free solutions nerve impulses invade the motor nerve terminals at the neuromuscular junction, but fail to release transmitter. In these conditions, strontium ions applied iontophoretically to a minute part of a junction, or to the whole muscle by bath application, restore to the nerve impulse its ability to release transmitter.2. As with calcium, the transmitter released in the presence of strontium is in the form of packages (quanta) whose release can be predicted from Poisson's Theorem.3. The mean number of quanta released by a nerve impulse increases with the concentration of strontium. Strontium is much less effective than calcium in equimolar concentrations.4. Transmitter quanta released in the presence of strontium evoke larger unit potentials than quanta released in the presence of calcium. The larger size of the Sr-unit potentials is caused by a prolongation of transmitter action, presumably due to a post-synaptic effect of strontium.5. Neuromuscular transmission was blocked in some fibres when the concentration of strontium was raised beyond 10 mM. This junctional block was presumably due to a failure in the propagation of nerve impulses.6. The post-stimulation increase in the frequency of miniature end-plate potentials, which is normally seen in calcium solutions, is also observed when calcium is substituted by strontium. The post-stimulation effect increases with the concentration of strontium.7. It is concluded that strontium can substitute for calcium in the process of quantal release of transmitter. The physico-chemical mechanism of this substitution remains unknown.

Animals↗
PubMed1969

Tetrodotoxin-resistant electric activity in presynaptic terminals.

1. The electric properties of the giant synapse in the stellate ganglion of the squid have been further investigated.2. During tetrodotoxin (TTX) paralysis, a local response can be elicited from the terminal parts of the presynaptic axons after intracellular injection of tetraethyl ammonium ions (TEA).3. The response is characterized by an action potential of variable size and duration, whose fall is often preceded by a prolonged plateau. The response, especially the duration of the plateau, is subject to ;fatigue' during repetitive stimulation.4. The TTX-resistant form of activity is localized in the region of the synaptic contacts, and shows a marked electrotonic decrement even within less than 1 mm from the synapse. It is found only on the afferent, not on the efferent, side of the synapse.5. During the plateau of the response, the membrane resistance is greatly reduced below its resting value.6. The response depends on presence of external calcium and increases in size and duration with the calcium concentration. Strontium and barium substitute effectively for calcium. Manganese and, to a lesser extent, magnesium, counteract calcium and reduce the response. The response also declines, and ultimately disappears, if sodium is withdrawn for long periods.7. The relation of the local TTX-resistant response to the influx of calcium ions and to the release of the synaptic transmitter is discussed.

Action Potentials↗
PubMed1969

Spontaneous and evoked activity of motor nerve endings in calcium Ringer.

1. Electrical activity of neuromuscular junctions of the frog was studied in a medium (Ca-Ringer) whose Na ions had been entirely replaced by Ca.2. Spontaneous miniature end-plate potentials (m.e.p.p.s) of reduced amplitude are recorded in this abnormal ionic environment, and graded end-plate potentials can be elicited by applying depolarizing current pulses to the pre-junctional parts of the nerve.3. Addition of 5 mM tetraethylammonium (TEA) to the Ca-Ringer causes the appearance, in almost all-or-none fashion, of very large e.p.p.s (up to 45 mV in amplitude) in response to nerve stimulation.4. These ;giant' e.p.p.s occur despite the curarizing action of TEA (and its depressing effect on the amplitude of m.e.p.p.s) and they persist after application of tetrodotoxin.5. After several hours exposure to Ca-Ringer, spontaneous end-plate activity gradually declines, and eventually evoked e.p.p. responses fail. On return to normal Na-Ringer, spontaneous end-plate activity is quickly resumed, but the potentials have an abnormal, very wide, amplitude distribution.6. The results are discussed, in conjunction with relevant work on the squid giant synapse, in terms of the ;calcium hypothesis' of transmitter release.

Animals↗
PubMed1968

The role of calcium in neuromuscular facilitation.

1. The hypothesis is put forward that a residue of the ;active calcium' which enters the terminal axon membrane during the nerve impulse is responsible for short-term facilitation.2. This suggestion has been tested on the myoneural junction by varying the local calcium concentration so that during the first of two nerve impulses [Ca](o) is either much lower than, or raised to a level approaching that, during the second impulse. Facilitation is much larger in the latter case, which is in accordance with the ;calcium hypothesis'.3. A short pulse of depolarization focally applied to the junction is followed by a brief period of very intense facilitation. This can be seen in the tetrodotoxin-treated preparation, e.g. by lengthening the depolarization from 1 to 2 msec which can cause a more than fifty-fold increase in transmitter release. This large ;early facilitation' (which presumably occurs also during the course of a normal action potential) is discussed in relation to the ;calcium hypothesis'.

Animals↗
PubMed1968

The effect of local blockage of motor nerve terminals.

1. Electrophoretic application of tetrodotoxin (TTX) was used to study the effect of localized blockage of impulses in motor nerve terminals.2. Under suitable conditions it can be shown that local production of end-plate potentials ceases distal to the site of TTX application, while it continues without diminution at proximal sites of the same terminal arborization.3. It is concluded that electrotonic spread of an action potential wave along a motor nerve terminal is insufficient to elicit transmitter release. Active propagation in the terminals is an essential requirement for neuromuscular transmission.

Action Potentials↗