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M R Bennett

Publications and source records attributed to M R Bennett.

At least 271 records · Page 15Linked to original sources
PubMed1979

The effect of calcium ions on the secretion of quanta evoked by an impulse at nerve terminal release sites.

A study has been made of the effects of calcium ions on the number of quanta secreted from all the release sites at an amphibian motor nerve terminal recorded with an intracellular microelectrode (m) compared with the number secreted simultaneously from a small number of release sites recorded with an extracellular microelectrode (me). If the endplate potential was made subthreshold by lowering the external calcium concentration ([Ca]o less than or equal to 0.4 mM), it was possible to find small groups of release sites for which me was comparable to m, indicating considerable nonuniformity in the probability of release of a quantum at different groups of release sites (Pe) in a given [Ca]o. Increasing [Ca]o in the range from 0.25 to 0.4 mM increased the probability of release of a quantum at groups of release sites (Pe), independent of the initial value of Pe, and the dependence of Pe on [Ca]o followed a fourth power relationship. A conditioning impulse enhanced the probability of release of a quantum by a subsequent test impulse at release sites, if Pe was less than 1.0 during the conditioning impulse. It is shown that the present observations regarding the dependence of Pe on [Ca]o and on conditioning impulses can be quantitatively predicted from previous observations regarding the dependence of the binomial parameters m, p, and n on [Ca]o and on conditioning impulses determined with intracellular electrodes, if the probability of secretion of a quantum at a release site (Pj) is different for different release sites and Pj is distributed as a beta random variable.

Action Potentials↗
PubMed1979

Development of the segmental innervation of the chick forelimb.

A number of recent studies have shown that during embryonic development the initial innervation of a target structure may be made up, in part, by axons which do not form part of the mature innervation of that structure. In the present study we have examined the motor innervation of the major muscles of the chick forelimb at different stages of development using HRP-uptake-labelling of motoneurons, electrophysiological recording and measurement of muscle contraction. In the mature White Leghorn chick the major contribution to the motor innervation of the forelimb is from spinal segments 14, 15 and 16. Using the HRP-labelling technique we have shown that at stages 26-29 of development motoneurons in segments 12-17 have axon terminals in the presumptive biceps muscle. Between stages 30 and 35, however, the axon terminals arising from segments 12, 13, 16 and 17 are lost, leaving the mature innervation from segments 14 and 15. We have also observed the loss of innervation of the biceps muscle by segment 16 using electrophysiological recording of compound action potentials in the biceps nerve and by measurement of the local contraction of the biceps muscle in response to stimulation of the segmental nerves. Similar changes in the innervation of the triceps, extensor metacarpi radialis, flexor carpi ulnaris and flexor digitorum profundus muscles have also been observed. These results are discussed in relation to the hypothesis that (i) the motoneuron pools and muscles in the developing spinal cord and forelimb are matched, (ii) that some axons which arrive in a particular muscle during early development are unable to form a stable connexion and (iii) that the inability of an axon terminal to form a stable connexion in a muscle results in the death of the motoneuron. Intracellular recording from muscle cells at stage 35 shows that the synaptic site on each cell is innervated by about three separate axons. Over the next few stages, however, all but one of the innervating axons is lost. From our contraction studies it is clear that the removal of the excess axon terminals after stage 35 is not associated with the establishment of the mature segmental innervation pattern of the muscle.

Action Potentials↗
PubMed1979

Segmental innervation of the chick forelimb following embryonic manipulation.

A number of studies have shown that the segmental innervation of some muscles in the developing limb undergoes some modification during the earliest stages of ontogeny. These observations can be interpreted in support of the hypothesis that the motor axons and muscles are matched during this period of development. As a further test of this suggestion we have made a quantitative examination of the motor innervation of the chick forelimb under conditions of controlled abnormal development. Embryos were surgically manipulated at stages before the motor axons invade the limb. The operations were controlled such that forelimbs were induced with segments deleted or reduplicated or simply that a segment of the spinal cord had been deleted. In preparations with abnormal limbs the motor innervation of the muscles present was the same as for those muscles in the normal limb. Where a spinal segment had been deleted the limbs developed normally and their innervation was completed by the remaining brachial segments. These results suggest that any particular matching property of a developing muscle does not develop as a consequence of its position in the limb relative to those segments of the limb proximal to it. Furthermore, that some muscles which are normally innervated by two spinal segments can be completely innervated by one of those spinal segments, in the absence of the other, suggests that any matching between growing axons and developing muscle cells is hierarchical rather than strictly all-or-nothing.

Animals↗
PubMed1977

The formation and regression of synapses during the re-innervation of axolotl striated muscles.

1. A study has been made of the formation and regression of synapses formed by spinal nerves 16 and 17 in axolotl hind-limb flexor muscles following the severing of nerve 16, using histological, ultrastructural and electrophysiological techniques. 2. Axolotl hind-limb flexor myofibres possessed 'en plaque' end-plates from either spinal nerve 16 or 17 or both at intervals of about 1000 micronm along their length; the myofibre's length constant was about 700 micronm allowing electrophysiological observations of at least two of these synapses during a single impalement; transmitter release at these synapses could be described by binomial statistics and in a given set of ionic conditions the binomial statistic parameter n was directly proportional to the size of the nerve terminals whilst the binomial statistic parameter p was invariant to changes in nerve terminal size. 3. The distribution of synapses formed by spinal nerves 16 and 17 in different sectors of the axolotl hind-limb flexor muscles was determined from a study of evoked end-plate potentials; the middle and proximal sectors of the flexor muscles contained myofibres which received an innervation from nerve 16 only, whereas the sectors surrounding these contained myofibres innervated either by nerve 16 or nerve 17 or by both nerves. 4. Six days following the severing of spinal nerve 16, evoked transmitter release from the synapses formed by this nerve had failed; transmission was subsequently recorded at a few synapses formed by nerve 17 in the middle and proximal sectors of the flexor muscles which are not normally innervated by this nerve and these synapses had a low n; during the succeeding four weeks the value of n at the synapses increased to a size about 70% that of the terminals normally formed by nerve 16 at these sites. 5. Four weeks after severing nerve 16, myofibres which possessed synapses formed by nerve 17 also possessed synapses from re-innervating nerve 16 and these were sometimes formed at the same synaptic sites as those occupied by nerve 17. 6. In the subsequent sixteen weeks, the n value of synapses formed by nerve 17 declined whilst the n values of synapses formed by re-innervating nerve 16 on the same myofibres matured to their control size. 7. It is suggested that on severing nerve 16 collateral sprouting of nearby intact nerve 17 occurs and these collateral sprouts innervate the denervated synaptic sites, although the sprouts arenot as well matched to the denervated synaptic sites as are the original nerve terminals; thus if nerve 16 returns it preferentially forms synapses at its original synaptic sites, and the collateral synapses formed by nerve 17 regress.

Ambystoma↗
PubMed1977

The effect of calcium ions and temperature on the binomial parameters that control acetylcholine release by a nerve impulse at amphibian neuromuscular synapses.

1. A study has been made of the effects of changing the external calcium concentration, [Ca](o), and the temperature on both the number of quanta available for release by the nerve impulse (n) as well as the increase in release probability of a quantum p(t) during the release period (from 0 to T) following a nerve impulse at synapses in amphibian striated muscle.2. When [Ca](o) was increased in the low range from 0.25 to 0.4 mM at 18 degrees C, the average quantal content of the e.p.p. (m) increased as the fourth power of [Ca](o) and this was primarily due to a third power dependence of n on [Ca](o); the dissociation constants and power dependence of n on calcium determined in the [Ca](o) range from 0.25 to 1.0 mM were successfully used to predict the changes in size of the e.p.p. in the very high [Ca](o) range from 1 to 10 mM. When the temperature was increased from 7 to 18 degrees C in a [Ca](o) of 0.6 mM or 0.35 mM, n increased with a Q(10) of 2.5.3. When [Ca](o) was increased in the range from 0.25 to 1.0 mM at 18 degrees C, the probability that a quantum initially available for release is released during the release period (p(T)) was very sensitive to [Ca](o), increasing as the third power of [Ca](o) and with a dissociation constant of 0.13 mM. When the temperature was increased from 7 to 18 degrees C in a [Ca](o) of 0.6 mM or 0.35 mM, p(T) decreased.4. The histograms of latencies of individual quanta following a nerve impulse was very temperature dependent: the time to peak of the histograms (i.e. the interval in which most quanta fell) had a Q(10) of over 4 as did the time constant of decline of the histograms in the temperature range from 7 to 18 degrees C.5. The average number of quanta released up to time t during the release period following a nerve impulse, namely np(t), was well described by a stochastic process in which p(t) was determined by two reactions; one of these reactions released available quanta from the nerve terminal whilst the other made some of the available quanta unavailable for release by the nerve impulse.

Acetylcholine↗
PubMed1977

The effects of calcium ions on the binomial parameters that control acetylcholine release during trains of nerve impulses at amphibian neuromuscular synapses.

1. A study has been made of the effects of changing the external calcium concentration [Ca](o) on the binomial parameters p and n that control the average quantal content (m) of the end-plate potential (e.p.p.) during trains of nerve impulses at synapses in amphibian striated muscle.2. In high external calcium concentrations (0.4 mM </= [Ca](o) < 1.0 mM) the increase in m of a test impulse following a conditioning impulse at different intervals (< 100 msec) was due to an increase in the number of quanta available for release, n; the increase in m of successive e.p.p.s in a short high frequency train was primarily due to an increase in n.3. In high external calcium concentrations (1.0 mM </= [Ca](o) < 10 mM) there was a decrease in m of a test impulse following a short high frequency conditioning train (4-5 impulses, 20-100 Hz) at different intervals (200 msec < 5 sec) and this was due to a decrease in the number of quanta available for release, n; in a long high frequency train (20 impulses, 20-100 Hz) there was an increase in m for the first few successive e.p.p.s followed by a depression of m which eventually reached a steady state and these changes in m were due to changes in n; the higher the frequency the greater was the depression in n during the steady-state period.4. In high calcium concentrations, the steady-state m reached in the first 20 impulses during continual stimulation at high frequency gave way to a decline in m over several minutes until a new depressed steady-state value of m was reached and this was maintained during the longest periods of stimulation (30 min); this decline in m was primarily due to a decline in the number of quanta available for release.5. These changes in the number of quanta available for release during trains of impulses are predicted in terms of a hypothesis in which facilitation is due to the accumulation of a residual calcium-receptor complex in the nerve terminal that determines the fraction of a pool of quanta which contributes to n, and depression is due to a decrease in the number of quanta in this pool.

Acetylcholine↗
PubMed1976

The effect of calcium ions on the binomial statistic parameters that control acetylcholine release at preganglionic nerve terminals.

1. A study has been made of the effects of changing [Ca]O and [Mg]O on the binomial statistic parameters p and n that control the average quantal content (m) of the excitatory post-synaptic potential (e.p.s.p.) due to acetylcholine release at preganglionic nerve terminals. 2. When [Ca]O was increased in the range from 0-2 to 0-5 mM, p increased as the first power of [Ca]O whereas n increased as the 0-5 power of [Ca]O; when [Mg]O was increased in the range from 5 to 200 mM, p decreased as the first power of [Mg]O whereas n decreased as the 0-5 power of [Mg]O. 3. The increase in quantal release of a test impulse following a conditioning impulse was primarily due to an increase in n; the increase in quantal content of successive e.p.s.p.s in a short train was due to an increase in n and p, and the increase in n was quantitatively described in terms of the accumulation of a Ca-receptor complex in the nerve terminal. 4. The decrease in quantal content of successive e.p.s.p.s during long trains of impulses over several minutes was primarily due to a decrease in n. These results are discussed in terms of an hypothesis concerning the physical basis of n and p in the release process.

Acetylcholine↗
PubMed1975

An electrophysiological analysis of the effects of reserpine on adrenergic neuromuscular transmission.

1 An electrophysiological study has been made of the effects of depleting synaptic vesicles (i.e. small vesicles less than 60 nm diameter) of their transmitter with reserpine on the quantity of transmitter released by nerve impulses, using the amplitude of the synaptic potential as a measure of transmitter release. 2 Pretreatment of adrenergic nerve terminals with reserpine sufficient to deplete the terminals of 70% of their noradrenaline (NA) did not change the total number of synaptic vesicles in the terminals, but did reduce the number with a large granular core as well as the quantity of NA released by a single nerve impulse by 80%. 3 Pretreatment of adrenergic nerve terminals with reserpine and iproniazid, to decrease vesicular NA but enhance cytoplasmic NA, had the same effect on synaptic vesicles and on the NA released by a single nerve impulse as did reserpine alone. 4 During a short train of impulses at high frequencies in reserpine pretreated terminals, the quantity of NA released by successive impulses increased until a steady-state release was reached comparable to that in untreated preparations. This facilitated release could be quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 5 These results are consistent with the idea that each quantum of transmitter is stored in a synaptic vesicle, and that these may be released by nerve impulses directly from the terminal by a process of exocytosis.

Animals↗
PubMed1975

An electrophysiological analysis of the effects of amine-uptake blockers and alpha-adrenoceptor blockers on adrenergic neuromuscular transmission.

1 An electrophysiological study has been made of the effects of either blocking noradrenaline (NA) uptake or alpha-adrenoceptors on conduction in adrenergic preterminal axons and on NA release. 2 The excitatory junction potential (e.j.p.) evoked by a single stimulus increased slightly in duration (maximum 20%) in the presence of high concentrations of desipramine or cocaine (larger than or equal to 1 mug/ml) but there was no change in the spontaneous miniature excitatory junction potential (m.e.j.p.s); the single compound preterminal action potential was decreased in amplitude by a maximum of 10%. The e.j.p., m.e.j.p. and the terminal action potential were not altered by lower concentrations of these drugs (less than mug/ml). 3 The increased decline of the e.j.p. amplitude observed during the first few hundred impulses at high frequencies (10 Hz) in the presence of desipramine or cocaine was accompanied by a similar decline in the amplitude of the preterminal compound action potential, suggesting that the latter gave rise to the former. 4 These observations suggest that the action on post-synaptic alpha-adrenoceptors of NA released by single impulses is terminated by diffusion, and that any NA which is subsequently taken up into nerves is metabolized. 5 All the alpha-adrenoceptor blocking drugs tested reversed the normal depression in e.j.p. amplitude observed during the first few hundred impulses at high frequencies to facilitation; this was unaccompanied by any changes in the preterminal compound action potential. 6 Alpha-Adrenoceptor blocking drugs did not alter the potentiating effect which a conditioning impulse had on the amplitude of the e.j.p. evoked by a subsequent test impulse. The facilitated release of NA during trains of impulses was quantitatively predicted in terms of the addition of the individual potentiations introduced by each impulse in the train. 7 It is suggested that if there is an auto-inhibition of NA release, then it is unlikely that the pre- and post-synaptic alpha-adrenoceptors are identical.

Action Potentials↗
PubMed1975

An electrophysiological analysis of the effect of Ca ions on neuromuscular transmission in the mouse vas deferens.

1 A study has been made of the effects of changing the external calcium concentration [Ca]0 and the external magnesium concentration [Mg]0 on the synaptic potential due to noradrenaline release. 2 When [Ca]0 was varied in the range 0.7 to 1.8 mM, the synaptic potential increased as about the second power of [Ca]0. 3 Increasing [Mg]0 depressed the synaptic potential; however, variation of [Ca]0 in the presence of high [Mg]0 did not significantly change the power relationship between the synaptic potential and [Ca]0. 4 The facilitated increase in the synaptic potential during short trains of impulses at different frequencies was quantitatively predicted on the assumption that each impulse leaves residual Ca ions bound to release receptors in the nerve terminal.

Action Potentials↗
PubMed1975

The effect of calcium ions on the binomial statistic parameters which control acetylcholine release at synapses in striated muscle.

A study has been made of the effects of changing [Ca]O and [Mg]O on the binomial statistic parameters p and n which control the average quantal content (m) of the synaptic potential due to acetylcholine release. 2. When [Ca]O was varied in the range 0-1 to 1-0 mM, p increased as the first power of [Ca]O whereas n increased as the third power of [Ca]O. 3. Increasing [Mg]O depressed both p and n, however variations of [Ca]O in the presence of high [Mg]O did not significantly change the power relationship between either p and [Ca]O or between n and [Ca]O. 4. The facilitated increase in m during a short train was due to an increase in n, whereas the post-tetanic increase in m during a tetanus was due to an increase in p. These results are considered in terms of the role of Ca ions in facilitation and post-tetanic potentiation.

Acetylcholine↗
PubMed1975

The formation of synapses in amphibian striated muscle during development.

1. A study has been made of the formation of synapses in developing reinnervated and cross-reinnervated amphibian twitch muscles which receive either a focal (iliofibularis) or a distributed (sartorius) innervation from 'en plaque' nerve terminals using histological, ultrastructural and electrophysiological techniques. 2. During the development of the tadpole through metamorphosis to the adult frog, the sartorius myofibres increased in length at about twice the rate of the iliofibularis myofibres, due to a fast rate of growth at their insertions on to the pelvic tendon. 3. The short iliofibularis and sartorius myofibres of young tadpoles (800 mum long) possessed only a single synapse and the iliofibularis myofibres did not receive any further innervation during development. However the sartorius myofibres received further transient innervation on the new muscle laid down during development at the fast growing pelvic insertion, until the distance between the original synapse formed on the myofibres and the synapse at the pelvic end of the muscle was about 12 mm. 4. During development synapses possessed either skewed, multimodal, or unimodal m.e.p.p. amplitude-frequency distributions; the intervals between m.e.p.p.s. were not distributed randomly according to a Poisson process, as m.e.p.p.s. of similar amplitudes tended to be separated by very short intervals; the unit-size e.p.p. had a similar amplitude-frequency distribution as the m.e.p.p.s. if these had a unimodal distribution. 5. Reinnervation or cross-reinnervation of the sartorius and the iliofibularis muscles in adults or at a late stage of development simply reconstituted the normal focal and distributed innervation patterns of the muscles, as found in the control muscles of the contralateral and unoperated legs. 6. These observations on synapse formation in amphibia are consistent with the hypothesis that during development the axon making the initial synaptic contact on the muscle cells induces a property over a length of muscle membrane adjacent to this site which makes it refractory to synapse formation; thus during reinnervation or cross-reinnervation of adult muscles this refractory property constrains synapse formation to these sites.

Amphibians↗
PubMed1974

The formation of synapses in regenerating mammalian striated muscle.

1. A histological and electrophysiological study has been made of the formation of synapses in soleus and extensor digitorum longus muscles of adult rats regenerating from minced muscle fragments.2. In the first 8 days of regeneration, myoblast and myotubes formed within the basement membranes of degenerating myofibres.3. Eleven- to fourteen-day regenerates contained fasicles of myotubes and myofibres and both nerves and spontaneous miniature end-plate potentials (m.e.p.p.s) were observed for the first time, although very few synapses show evoked end-plate potentials (e.p.p.s).4. Eighteen- to twenty-six-day regenerates contained. myofibres on which only a single end-plate could be detected; 30% of these synapses had a normal amplitude-frequency distribution of m.e.p.p.s and subthreshold e.p.p.s whilst at the remainder the e.p.p. was either suprathreshold or did not occur.5. Thirty- to sixty-day regenerates contained myofibres and end-plates with the same morphological and functional characteristics as those in normal muscle.

Animals↗
PubMed1974

A statistical analysis of the release of acetylcholine at newly formed synapses in striated muscle.

1. A statistical analysis has been made of the changes in the binomial parameters n and p during transmitter release from motor-nerve terminals when synapses are forming in either regenerating or reinnervated mammalian muscle.2. The amplitude-frequency distribution of e.p.p.s evoked by a single impulse was well predicted by binomial statistics at all junctions analysed allowing values of n and p to be determined. At most of these junctions, p > 0.5 and Poisson statistics did not predict the observed distributions at all.3. During the changes in quantal content which occur during short trains of impulses or during continual stimulation over minutes, no significant change in p was detected. Changes in quantal content of the e.p.p. were therefore determined by n.

Acetylcholine↗
PubMed1974

The formation of synapses in striated muscle during development.

1. A study has been made of the formation of synapses in developing striated muscles which receive either a focal (the rat hemidiaphragm) or a distributed (the avian anterior latissimus dorsi) innervation using histological, ultrastructural and electrophysiological techniques.2. In the developing diaphragm only a single synaptic contact was initially established at random along the length of the short (300 mum) myotubes by a single axon; in the developing ALD more than one synaptic contact could be established initially along the length of the long (2500 mum) myotubes by axons, but the distance between these was never less than 170 mum.3. Each synapse established by the initial axonal contact in either the diaphragm or the ALD subsequently received a multiple innervation from further exploring axons in the muscles, and all such additional innervation of muscle cells was constrained to the sites of the initial synaptic contacts; this multiple innervation of synaptic sites was lost in the subsequent 4 weeks.4. It is suggested that the axon forming the initial synaptic contact on myotubes induces a property over an adjacent length of myotube which makes its membrane refractory to synapse formation over this length; this characteristic length is longer for axons forming a focal innervation than it is for those forming distributed innervation.

Acetylcholine↗