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K L Magleby

Publications and source records attributed to K L Magleby.

71 records · Page 4Linked to original sources
PubMed1980

Facilitation, augmentation, and potentiation of synaptic transmission at the superior cervical ganglion of the rabbit.

The effect of repetitive stimulation on synaptic transmission was studied in the isolated superior cervical ganglion of the rabbit under conditions of reduced quantal content. Excitatory postsynaptic potentials (EPSP) were recorded with the sucrose gap technique to obtain estimates of transmitter release. Four components of increased transmitter release, with time constants of decay similar to those observed at the frog neuromuscular junction at 20 degrees C, were found in the ganglion at 34 degrees C: a first component of facilitation, which decayed with a time constant of 59 +/- 14 ms (mean +/- SD); a second component of facilitation, which decayed with a time constant of 388 +/- 97 ms; augmentation, which decayed with a time constant of 7.2 +/- 1 s; and potentiation, which decayed with a time constant of 88 +/- 25 s. The addition of 0.1-0.2 mM Ba2+ to the Locke solution increased the magnitude but not the time constant of decay of augmentation. Ba2+ had little effect on potentiation. The addition of 0.2-0.8 mM Sr2+ to the Locke solution appeared to increase the magnitude of the second component of facilitation. Sr2+ had little effect on augmentation or potentiation. These selective effects of Ba2+ and Sr2+ on the components of increased transmitter release in the rabbit ganglion are similar to the effects of these ions at the frog neuromuscular junction. Although the effects of Ba2+ and Sr2+ are similar in the two preparations, the magnitudes of augmentation and the second component of facilitation after a single impulse were about 6-10 times greater in the rabbit ganglion than at the frog neuromuscular junction. These results suggest that the underlying mechanisms in the nerve terminal that give rise to the components of increased transmitter release in the rabbit ganglion and frog neuromuscular junction are similar but not identical.

Animals↗
PubMed1980

Nickel and calcium ions modify the characteristics of the acetylcholine receptor-channel complex at the frog neuromuscular junction.

1. Miniature end-plate currents (m.e.p.c.s) and acetylcholine induced current noise were recorded from the cutaneous pectoris muscle of the frog with the voltage-clamp technique. Analysis of current noise was used to estimate mean single channel current and the mean lifetime of an open channel. 2. Adding Ni2+ or Ca2+ to the bathing solution reduced the amplitude of the m.e.p.c.s. Ten mM-Ni2+ decreased the amplitude 64%, while raising Ca2+ from 2 to 10mM decreased the amplitude 35%. 3. The decreased amplitude of the m.e.p.c. in Ni2+ and increased Ca2+ can be explained by a decrease in single channel current. Ten mM-Ni2+ decreased mean single channel current 64% while raising Ca2+ from 2 to 10 mM decreased single channel current 28%. 4. The decrease in single channel current was due to a decrease in the driving potential and single channel conductance. Ten mM-Ni2+ and Ca2+ shifted the reversal potential for the m.e.p.c. about 10 mV negative from the control value of -4.6 mV; at the same time single channel conductance was decreased 59% in Ni2+ and 18% in increased Ca2+. 5. In contrast to the similar direction of effects of Ni2+ and Ca2+ on m.e.p.c. amplitude, reversal potential, and single channel conductance, Ni2+ and Ca2+ had different effects on m.e.p.c. time course. Ten mM-Ni2+ increased the time constant of m.e.p.c. decay 80% while raising Ca2+ from 2 to 10 mM decreased the time constant of decay 17%. 6. Ni2+ and Ca2+ also had different effects on single channel lifetimes. Ten mM-Ni2+ increased channel lifetime about 50%, while raising Ca2+ from 2 to 10 mM did not significantly affect channel lifetime. 7. These results suggest that changes in single channel lifetime and conductance due to ionic influences are not necessarily tightly coupled. The results also suggest that the effects of both Ni2+ and Ca2+ on channel lifetime cannot be accounted for in terms of a simple surface potential hypothesis.

Acetylcholine↗
PubMed1976

Augmentation: A process that acts to increase transmitter release at the frog neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded from frog neuromuscular junctions bathed in Ringer solution containing increased Mg and decreased Ca to reduce transmitter release. Conditioning and testing stimulation was applied to the nerve to study a previously uncharacterized process which acts to increase e.p.p. amplitudes. We will refer to this process as augmentation. 2. Following repetitive stimulation augmentation decayed approximately exponentially over most of its time course with a mean time constant of about 7 sec (range 4-10 sec) which is intermediate in duration between the time constants for the decay of facilitation and potentiation. 3 . The magnitude of agumentation increased with the duration of the conditioning stimulation. Assuming a multiplicative relationship between augmentation and potentiation, values of the magnitude of augmentation ranged from 0-3 to 0-6 following 50 impulses at 20/sec to 0-5-7-8 following 600 impulses at 20/sec. (An augmentation of 0-3 and 7-8 would increase e.p.p. amplitudes 1-3 and 8-8 times, respectively.) 4. The time constant characterizing the decay of augmentation remained relatively constant as the duration of the conditioning stimulation was increased. 5. Augmentation as well as facilitation and potentiation resulted from an increase in the number of quanta of transmitter released from the nerve terminal. 6. Augmentation decayed faster at higher temperatures with a mean temperature coefficient, Q10, of about 3-8. The corresponding Q10 for the decay of potentiation was found to be about 2-4. 7. It is concluded that augmentation can be a significant factor in increasing transmitter release and will therefore have to be accounted for when studying the effects of repetitive stimulation on the function of the nerve terminal or when formulating models of transmitter release.

Animals↗
PubMed1976

Long term changes in augmentation, potentiation, and depression of transmitter release as a function of repeated synaptic activity at the frog neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded from frog neuromuscular junctions under conditions of low quantal content to study the long-term effects of repeated synaptic activity on transmitter release. 2. The nerve terminal was presented with 30-100 successive conditioning-testing trials applied once every 7-10 min over a 4-16 hr perod. Each conditioning-testing trial consisted of a 200-600 impulse conditioning train followed by a series of testing impulses. The magnitudes and time constants of decay of augmentation and potentiation following each successive conditioning train were determined by measuring the e.p.p. amplitudes resulting from the testing impulses. 3. The magnitude of augmentation immediately following the conditioning trains increased an average of 3-4 times (range 1-20) with sucessive trials. 4. As the magnitude of augmentation increased with successive trials the decay of augmentation deviated from a simple exponential, decaying faster immediately after the conditioning train. This faster decay led to a 20% decrease with successive trials in estimates of the time constant obtained from the first 10 or 20 sec of the decay of augmentation. The deviation of the decay of augmentation from a simple exponential could be accounted for if augmentation is related to the 4th power of some substance which decays with a simple exponential time course. Some alternative explantations for the non-exponential decay of augmentation are also discussed. 5. The magnitude of potentiation increased or decreased about 25% with successive trials. 6. The time constant characterizing the decay of potentiation inceased an average of 1-5 times (range 0-8-5 times) with successive trials. 7. The increase in the magnitude of augmentation with successive trials was accompanied by a similar increase in the magnitude of the e.p.p. amplitudes during the conditioning trains, suggesting that augmentation develops during the conditioning train. In some preparatons augmentation appeared to be the major factor acting to increase e.p.p. amplitudes during the conditioning train, having a greater effect than facilitation or potentiation. 8. If a sufficiently large number of successive trials were applied, a depression of e.p.p. amplitudes developed during the conditioning trains and estimates of the magnitude of potentiation following the depressed conditioning trains were reduced...

Animals↗
PubMed1976

Stimulation-induced factors which affect augmentation and potentiation of trasmitter release at the neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded from frog sartorius neuromuscular junctions under conditions of decreased transmitter release to study the effect of repetitive stimulation on augmentation and potentiation of transmitter release. 2. The magnitudes and time constants of decay of augmentation and potentiation were determined both following a primary conditioning train and following an identical secondary conditioning train applied from 30 to 170 sec after the primary conditioning train. 3. The magnitude of augmentation following the secondary conditioning trains was increased over that following the primary conditioning trains even though augmentation, with a time constant of decay of about 7 sec, had decayed to insignificant levels before the onset of the secondary trains. This increase in augmentation was not due to a change in its rate of decay during the secondary trains. 4. The increased magnitude of augmentation can be described as arising from an expression factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-6 +/- 1-2 (S.D. of observation) (the magnitude of augmentation is increased 2-6 times) and decays approximately exponentially with a time constant of 90 +/- 50 (S.D. of observation) sec. The expression factor thus decays about ten times slower than augmentation. 5. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 2-8 +/- 1-0 (S.D. of observation) times increase in the magnitude of the expression factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 6. The expression factor, while increasing the magnitude of augmentation, had little or no effect on the magnitude of potentiation or on trasmitter release in the absence of augmentation. The expression factor decayed about twice as slowly as potentiation. 7. The time constants characterizing the decay of potentiation were greater following the secondary conditioning trains than following the primary conditioning trains. 8. The increased time constant for the decay of potentiation can be described as arising from a time constant factor which, for conditioning trains of 200 impulses at 20/sec, has an initial magnitude of 1-2 +/- 0-7 (S.D. of observation) (the time constant of potentiation is increased 2-2 times) and decays approximately exponentially with a time constant of 130 +/- 45 (S.D. of observation) sec. The time constant factor decayed about three times slower than potentiation. 9. Doubling the number of impulses in the primary conditioning train from 100 to 200 led to a 1-6 +/- 0-8 (S.D. of observation) times increase in the magnitude of the time constant factor, estimated by placing a 200 impulse secondary conditioning train 40 sec after the primary conditioning train. 10...

Animals↗
PubMed1975

Factors affecting the time course of decay of end-plate currents: a possible cooperative action of acetylcholine on receptors at the frog neuromuscular junction.

1. End-plate currents have been studied in gylcerol-treated frog sartorius nerve-muscle preparations with the voltage-clamp technique. 2. Adding the anticholinesterase prostigmine (3 muM) to the solution bathing the muscle caused a 2-7 (mean 3-3) times increase in the time constant of decay of end-plate currents. The anticholinesterase edrophonium (15 muM) also prolonged the time course of end-plate currents. 3. Pre-treatment of the preparation with collagenase, which leads to the removal of acetylcholinesterase in the synaptic cleft, prolongs the time course of end-plate currents. 4. Curare (1-2 muM), cobratoxin (0-13 muM), or alpha-bungarotoxin (0-13-0-26 muM) decreased the time constant of decay of end-plate currents in the presence of prostigmine. 5. These observations are consistant with the suggestion that repeated binding of acetylcholine (ACh) molecules to receptors as the ACh escapes from the synaptic cleft can contribute to the prolongation of end-plate currents which occurrs when acetylcholinesterase activity is eliminated. 6. Increasing the amount of transmitter released from the presynaptic nerve terminal leads to a prolongation of end-plate currents in the presence of prostigmine. 7. In the presence of prostigmine, the second of two end-plate currents (interval 2-10 msec) decays more slowly than the first. 8. ACh (1-40 muM) or carbachol (40 muM) applied in the solution bathing the muscle prolongs end-plate currents in the presence of prostigmine. 9. It is suggested on the basis of the observations described in paragraphs 6 to 8 that the time constant of decay of end-plate currents in the presence of prostigmine increases with increasing concentrations of ACh in the synaptic cleft. In the absence of prostigmine, increasing the concentration of ACh in the synaptic cleft did not change the time constant for decay of end-plate currents. 10. We interpret these results to suggest that ACh can have a cooperative action on receptors such that the association of ACh with one receptor (defined as binding a single ACh molecule) favours the binding or retention of ACh at other receptors. This implies that receptors can interact.

Acetylcholine↗
PubMed1975

A dual effect of repetitive stimulation on post-tetanic potentiation of transmitter release at the frog neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded with a surface electrode from frog neuromuscular junctions blocked with high Mg and low Ca to study post-tetanic potentiation(potentiation). 2. Potentiation is found to decay exponentially over most of its time course. 3. The time constant tsu(H) characterizing this exponential decay is a function of the previous history (frequency and duration) of stimulation. For example, tsu(H) increased from about 20 sec following a few impulses to over 70 sec following more than 1000 impulses. 4. A new method is presented to obtain estimates of the rise of potentiation (uncontaminated by facilitation or an intermediate facilitatory process) during repetitive stimulation. It is found that potentiation is present following short trains of impulses and continually increases in magnitude with the duration of the conditioning stimulation. Potentiation was at a maximum immediately following the conditioning trains. 5. The relationship between P(T), the magnitude of potentiation immediately following repetitive stimulation, and tsu(H), the time constant for the decay of this potentiation, is given by tsu(H)=Ae-P(T)/B, where A=19-8 plus or minus 5-1 sec (mean plus or minus S.D. of an observation) and B increases from 2.2plus or minus 2-1 to 5-7 plus or minus 2-7 as the stimulation rate increases from 5 to 30/sec. 6. The value of A in the above equation can be considered to represent the minimal time constant for the decay of potentiation--that is, the time constant for decay after a simgle impulse. 7. Evidence is presented for a afacilitatory process with a time constant of decay of about 3 sec which is intermediate in duration between facilitation and potentiation. 8. It is suggested that repetitive stimulation has a dual effect on potentiation; each impulse (1) adds an increment of potentiation and (2) increases tsu(H), the time constant for the decay of potentiation.

Action Potentials↗
PubMed1975

A quantitative description of tetanic and post-tetanic potentiation of transmitter release at the frog neuromuscular junction.

1. End-plate potential (e.p.p.s) were recorded with a surface electrode from frog neuromuscular junctions blocked with high Mg and low Ca to study post-tetanic potentiation (potentiation). 2. The magnitude of potentiation was not directly related to the number of conditioning impulses, but was a function of the frequency and duration of the conditioning stimulation. 3. Potentiation was always greater following an equal number of impulses delivered at a higher frequency of stimulation. 4. Plots of the magnitude of potentiation against the number of conditioning impulses would sometimes show an upward inflexion depending on the parameters of stimulation. 5. These experimental observations were described by a model based on the assumption (1) that potentiation is linearly related to a residual substance, R(t), which accumulates in the nerve terminal during repetitive stimulation, and (2) that each nerve impulse adds an identical increment, r, of this residual substance. The data were not described by assuming a 4th power relationship between potentiation and R(t). 6. The upward inflexion in potentiation (see paragraph 4) is described by the model as resulting from an increase in the time constant for the decay of potentiation as the magnitude of potentiation increases. 7. The increment of residual substance r added by each impulse was independent of the amount of transmitter released during the conditioning train. This increment typically increased transmitter release by amount 1% of the control level in the absence of potentiation. 8. Suggestions are given to explain why potentiation of transmitter release, which is thought to arise from an accumulation of Ca-2+ in the nerve terminal, can be described assuming a linear relationship between potentiation and R(t), the proposed substance responsible for potentiation, under experimental conditions in which a 3rd to 4th power relationship would be expected to exist between external Ca concentration and evoked transmitter release.

Animals↗
PubMed1973

The effect of repetitive stimulation on facilitation of transmitter release at the frog neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded from frog neuromuscular junctions blocked with high Mg and/or low Ca to characterize the processes underlying increased transmitter release during repetitive stimulation.2. There was a progressive increase in the amplitude of successive e.p.p.s during repetitive stimulation. Increasing the frequency or duration of stimulation increased this facilitation of e.p.p. amplitudes. Facilitation is defined as the fractional increase in amplitude of a test e.p.p. over a control.3. By assuming that each impulse in a train contributes an identical increment of facilitation that sums linearly with the facilitation contributed by the previous impulses, estimates of the facilitation contributed by a single impulse, f(t), were made from the incremental increase in e.p.p. amplitudes during repetitive stimulation. The average value of f(t) contributed by the first impulse in the train during stimulation at 20/sec is given by f(t) = 0.8 e(-t/50) + 0.12 e (-t/300) + 0.025 e(-t/3000),where t is in msec. The first two terms in this equation were independent of the stimulation rate used to determine f(t) while the coefficient of the third term was a function of the stimulation rate, decreasing 2 to 3 times when the stimulation rate was decreased from 20/sec to 1/sec.4. This linear facilitation model predicted growth of e.p.p. amplitudes during the first several hundred msec of repetitive stimulation. Thereafter, e.p.p. amplitudes were typically facilitated more than predicted by the linear model.5. Several new methods are presented which can be used to obtain estimates of the magnitude and time course of facilitation contributed by specific impulses during repetitive stimulation.6. It is found that the value of short-term f(t) in the tested range of 25-300 msec progressively increases during repetitive stimulation while its time course of decay remains unchanged. After 9 sec of stimulation at 20/sec, the short-term f(t) increased to 1.4 times control.7. The increase in short-term f(t) was independent of whether it was determined from a step increase or decrease in total facilitation, excluding the possibility that the observed increase in short-term f(t) resulted from a change in the rate of decay of facilitation.8. It is suggested with supporting data from the following paper (Magleby, 1973) that each impulse contributes two types of facilitation that are responsible for the growth of e.p.p.s during repetitive stimulation: a short-term facilitation with linear summation properties described by the first two terms in the expression in paragraph 3 and a long-term cumulative facilitation approximated by the third term. The long-term facilitation is expressed as an increase in both the short-term facilitation and in the base level of transmitter release. The relative contribution of these two expressions of the long-term facilitation to the third term is a function of the stimulation rate and is given by the ratio of facilitation to the base level of transmitter release.

Animals↗
PubMed1973

The effect of tetanic and post-tetanic potentiation on facilitation of transmitter release at the frog neuromuscular junction.

1. End-plate potentials (e.p.p.s) were recorded from frog neuromuscular junctions blocked with high Mg and/or low Ca.2. Estimates of f(t), the facilitation contributed by each impulse, were obtained during and following repetitive stimulation from the incremental change in e.p.p. amplitudes following step changes in the stimulation rate during the conditioning and testing trains.3. Estimates of f(t) increased during the conditioning stimulation and returned to control in the post-tetanic period. This increase in f(t) was proportional to the magnitude of tetanic or post-tetanic potentiation (PTP) present.4. These results are described by: [Formula: see text] where h(t)/h(c) is the e.p.p. amplitude at time t expressed in terms of the control, P(t) is potentiation, F(t) is facilitation and 1 is the base level of transmitter release. Thus, potentiation has a multiplicative (gain) effect on facilitation and the base level of transmitter release.5. PTP was present immediately following the conditioning train. However, if depression occurred during the conditioning train, PTP developed after a delay.6. It is suggested that facilitation and potentiation represent increases in two independent factors which act jointly to increase the probability of transmitter release.

Animals↗
PubMed1972

The effect of voltage on the time course of end-plate currents.

1. End-plate currents have been studied in glycerol-treated frog sartorius nerve-muscle preparations with the voltage clamp technique.2. End-plate currents follow a simple exponential time course over most of their declining phase.3. The rate constant alpha that characterizes this exponential decay depends upon membrane potential V according to the relationship alpha (V) = Be(AV), with A = 0.00795 +/- 0.00043 (S.E.) mV(-1) and B = 1.67 +/- 0.04 (S.E.) msec(-1).4. Voltage sensitivity decreases (that is, A in the above equation becomes smaller) as the recording and current-passing electrodes are moved away from the end-plate region.5. The voltage sensitivity of alpha is decreased by decreasing the gain of the voltage clamp amplifier.6. Changing the end-plate current amplitude by curare treatment, by increased calcium ion concentration, and by facilitation and depression has essentially no effect on end-plate current time course.7. When membrane potential is changed step-wise during the decaying phase of the end-plate conductance change, currents begin to decline with a rate constant alpha appropriate to the new membrane potential in less than 0.2 msec.8. Treatment with prostigmine methylsulphate in concentrations up to 50 mug/ml. slows end-plate current decay but has little effect on voltage sensitivity. That is, B in the above equation is decreased by prostigmine treatment, but A is relatively unaffected.

Action Potentials↗
PubMed1972

A quantitative description of end-plate currents.

1. End-plate currents have been studied in glycerol-treated frog sartorius nerve-muscle preparations with the voltage clamp technique.2. The effects of temperature on the decay rate of end-plate currents were investigated over a temperature range from 10 to 30.5 degrees C. The Q(10) for the decay constant of end-plate currents depends somewhat on membrane potential; at - 100 mV the decay constant has a Q(10) of 2.7.3. Peak end-plate current depends non-linearly on membrane potential with a decreasing slope conductance associated with hyperpolarization.4. The ;instantaneous' voltage-current relationship for end-plate channels was determined by causing step changes in membrane potential during end-plate current flow. This relationship appears to be linear.5. The interaction of acetylcholine with its receptor is viewed as being analogous to the first step in enzymic catalysis. On this view, acetylcholine binds to its receptor and induces a conformational change which is responsible for opening end-plate channels. By analogy to the first steps in the catalytic sequence of enzymes, the binding step is very rapid, almost diffusion-limited, and the conformational change is rate-limiting.6. Equations describing this process have been derived. Expressions for the rate constants have also been derived by considering changing dipole moments of the transmitter-receptor complex associated with the conformational change. As the transmitter-receptor complex is in the membrane field, different conformational states have different energies, and the rate of conformational change thus depends on membrane potential. The equations thus derived are shown to account adequately for the time course of end-plate conductance change.

Acetylcholine↗
PubMedDate not supplied

Inverse relationship of the durations of adjacent open and shut intervals for C1 and K channels.

Ion channels in cell membranes, whether voltage-dependent or activated by ligands, make repeated transitions among open and shut states during activity. Information about the number of states and the transitional pathways between them can be obtained from the durations of open and shut intervals, as transitions to states of different lifetimes result in intervals of different mean durations. If there is only one open conformation, or state, then the durations of open intervals would be independent of the durations of adjacent shut intervals. On the other hand, if a channel has two or more open states with different mean lifetimes, and if each open state is entered directly from a different shut state with a different mean lifetime, then the open intervals should be related to the adjacent shut intervals. We now report that the durations of adjacent open and shut intervals for both a C1 channel and a large conductance Ca-activated K channel in skeletal muscle are inversely related; shorter open intervals are adjacent to longer shut intervals. These findings indicate that two or more shut states make direct transitions to two or more open states, and suggest that the lifetimes of adjacent open and shut states are inversely related.

Animals↗
PubMedDate not supplied

Single apamin-blocked Ca-activated K+ channels of small conductance in cultured rat skeletal muscle.

Action potentials in many excitable cells are followed by a prolonged afterhyperpolarization that modulates repetitive firing. Although it is established that the afterhyperpolarization is produced by Ca-activated K+ currents, the basis of these currents is not known. The large conductance (250 pS) Ca-activated K+ channel (BK channel) is not a major contributor to the afterhyperpolarization in non-innervated skeletal muscle and some nerve cells, because apamin, a neurotoxic component of bee venom, abolishes the afterhyperpolarization but does not block BK channels, and 5 mM extracellular tetraethylammonium ion (TEA) blocks BK channels but does not reduce the afterhyperpolarization. We now report single-channel currents from small conductance (10-14 pS) Ca-activated K+ channels (SK channels) with the necessary properties to account for the afterhyperpolarization. SK channels are blocked by apamin but not by 5 mM external TEA (TEAo). They are also highly Ca-sensitive at the negative membrane potentials associated with the afterhyperpolarization.

Action Potentials↗