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Biomedical subjects

B Katz

Publications and source records attributed to B Katz.

At least 199 records · Page 11Linked to original sources

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.

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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 The response also declines, and ultimately disappears, if sodium is withdrawn for long periods.7.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.

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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.

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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'.

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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.

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The timing of calcium action during neuromuscular transmission.

1. When a nerve-muscle preparation is paralysed by tetrodotoxin, brief depolarizing pulses applied to a motor nerve ending cause packets of acetylcholine to be released and evoke end-plate potentials (e.p.p.s), provided calcium ions are present in the extracellular fluid.2. By ionophoretic discharge from a 1 M-CaCl(2) pipette, it is possible to produce a sudden increase in the local calcium concentration at the myoneural junction, at varying times before or after the depolarizing pulse.3. A brief application of calcium facilitates transmitter release if it occurs immediately before the depolarizing pulse. If the calcium pulse is applied a little later, during the period of the synaptic delay, it is ineffective.4. It is concluded that the utilization of external calcium ions at the neuromuscular junction is restricted to a brief period which barely outlasts the depolarization of the nerve ending, and which precedes the transmitter release itself.5. The suppressing effect of magnesium on transmitter release was studied by a similar method, with ionophoretic discharges from a 1 M-MgCl(2)-filled pipette. The results, though not quite as clear as with calcium, indicate that Mg pulses also are only effective if they precede the depolarizing pulses.

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A study of synaptic transmission in the absence of nerve impulses.

1. The axo-axonic giant synapse in the stellate ganglion of the squid has been used to study synaptic transmission.2. When nerve impulses have been eliminated with tetrodotoxin, synaptic transfer of potential changes can still be obtained by applying brief depolarizing pulses to the presynaptic terminal.3. Suitably matched pulses are as effective as the normal presynaptic spike in evoking post-synaptic potentials. The synaptic delay and the time course of the post-synaptic potential are very similar to that in the normal preparation.4. The synaptic transfer (input/output) characteristic has been studied under different experimental conditions. With brief (1-2 msec) current pulses, post-synaptic response becomes detectable when the presynaptic depolarization exceeds about 30 mV. The post-synaptic potential increases about tenfold with 10 mV increments of presynaptic depolarization.5. Calcium increases, magnesium reduces the slope of the synaptic transfer curve. The influences on this curve of (i) duration of the pulse, (ii) preceding level of membrane potential, (iii) position of recording electrode, (iv) rate of repetitive stimulation are described.6. After loading the synaptic terminal with tetraethylammonium ions, large inside-positive potentials can be produced in the terminal and maintained for many milliseconds.7. By raising the internal potential to a sufficiently high level, synaptic transfer becomes suppressed during the pulse, and the post-synaptic response is delayed until the end of the pulse.8. This observation is in accord with a prediction of the ;calcium hypothesis', viz. that inward movement of a positively charged Ca compound, or of the calcium ion itself, constitutes one of the essential links in the ;electro-secretory' coupling process of the axon terminal.

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