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A Trautmann

Publications and source records attributed to A Trautmann.

At least 91 records · Page 5Linked to original sources
PubMed1983

Tubocurarine, a partial agonist for cholinergic receptors.

The mode of action of curare, a well-known competitive antagonist of acetylcholine at the nicotinic receptor, was examined with the single channel recording technique. Curare can open cholinergic channels in rat myotubes, as suggested by Ziskind and Dennis (1978). Moreover another curare molecule can then block the curare-activated open channel, in line with previous results concerning such a mode of action. In adult rat muscle, the partial agonist activity of curare can also be demonstrated, though it is much weaker than in embryonic muscle. It is also shown that in adult muscle cell, the conductance of the channel (activated either by ACh or by curare) is 50-60 pS, i.e., higher than in the myotubes (35 pS).

Acetylcholine↗
PubMed1982

Curare can open and block ionic channels associated with cholinergic receptors.

Curare has long been regarded as a typical competitive antagonist of acetylcholine (ACh) at the vertebrate neuromuscular junction. Recently, however, it has been shown that curare can also block the channels opened by ACh at the frog neuromuscular junction as well as on rat and Aplysia neurones; moreover, curare is able to depolarize rat myotubes and thus behaves as an agonist for the cholinergic receptor of this preparation (see ref. 6). Using the single channel recording technique, we have now found that, on rat myotubes, curare can both open and block in the same cell the channels controlled by the cholinergic receptor.

Acetylcholine↗
PubMed1982

Desensitization at the frog neuromuscular junction: a biphasic process.

1. The desensitization of the cholinergic receptor has been investigated at the frog neuromuscular junction. The agonist was either perfused or applied by ionophoresis.2. In all situations, desensitization develops in two phases: a fast one, experimentally in the second range but likely to be briefer, and a slower one, which extends over tens of seconds.3. When the presence of the agonist is prolonged, desensitization approaches a steady state, estimated through the amplitude of a test response. In steady-state conditions, this amplitude depends upon the desensitizing agonist concentration. The dose-response curve for desensitization induced by carbachol (CCh) indicates that half of the receptors can be desensitized at room temperature in the presence of 2.3 mum-CCh. The shape of the curve suggests that one desensitized receptor can bind two CCh molecules.4. The recovery from desensitization, estimated with a repetitive test pulse, displays two exponential phases. The time constant of the fast phase is 11-12 sec, and 4-5 min for the slow phase, regardless of the concentration or the nature of the agonist (acetylcholine or carbachol).5. The factor which most strikingly affects the relative amplitudes of the fast and slow phases of recovery is the duration of the (desensitizing) agonist application. Desensitizations lasting a few seconds are followed by a ;fast' recovery, whereas the slow phase of recovery is prominent when the agonist has been applied for more than 2 min.6. The fast and slow phases of desensitization onset and offset are not due to independent causes but are coupled: in given conditions, the onset can be essentially fast, and the recovery slow.7. All our findings can fit in a cyclic scheme of desensitization, derived from the one of Katz & Thesleff (1957) with two modifications: whether activatable or desensitized, one receptor molecule would have two agonist binding sites; moreover, the desensitized receptor would exist in two distinct and interconverting conformations: D(1), giving rise to the fast phases of onset and offset, and D(2), responsible for the existence of the slow components of desensitization.

Acetylcholine↗
PubMed1981

Properties of end-plate channels in rats immunized against acetylcholine receptors.

1. Rats injected with purified acetylcholine receptors (AChR) extracted from electric organs of Torpedo marmorata showed clinical symptoms consistent with the development of experimental myasthenia gravis.2. Sera of rats with this disease contain high levels of anti-AChR antibodies. However, no simple correlation was found between antibody titre and miniature end-plate current (m.e.p.c.) amplitude.3. M.e.p.c.s. at the end-plates of rats injected with AChR (Anti-R), emulsified in complete Freund Adjuvant (CFA), were reduced to about one third the size of controls taken from rats injected only with CFA (Anti-CFA). Mean m.e.p.c. (Anti-R) = 0.73 +/- 0.06 nA; mean m.e.p.c. (Anti-CFA) = 2.43 +/- 0.12 nA (V(m) = -80 mV, T = 20 degrees C).4. The m.e.p.c. decay time constant, tau(m.e.p.c.), is similar at immunized and control rat end-plates. tau(m.e.p.c.) (Anti-R) = 1.32 +/- 0.06 msec; tau(m.e.p.c.) (Anti-CFA) = 1.31 +/- 0.06 msec (V(m) = -80 mV, T = 20 degrees C).5. The end-plate current decay time constant, tau(e.p.c.), is similar at immunized and control end-plates and in both cases depends exponentially on membrane potential. The change in membrane potential required to produce an e-fold change in tau(e.p.c.) is 102.0 +/- 5.72 mV at immunized (Anti-R) end-plates and 92.3 +/- 6.14 mV at control (Anti-CFA) end-plates at T = 10 degrees C.6. Acetylcholine noise was examined at immunized and control rat end-plates at 10 degrees C. Analysis of noise indicates that the single channel conductance, gamma, and mean channel life-time, tau(noise), are essentially unchanged by immunization against AChR. gamma (Anti-R) = 13.15 +/- 0.53 pS; gamma (Anti-CFA) = 12.50 +/- 0.50 pS; tau(noise) (Anti-R) = 2.9 +/- 0.18 msec; tau(noise) (Anti-CFA) = 2.68 +/- 0.14 msec (V(m) = -80 mV, T = 10 degrees C).7. Mean quantal content and Ca(2+) dependence of the end-plate potential are unchanged at immunized end-plates.8. It is concluded that at immunized end-plates the number of activated receptor-channel complexes is reduced without modification of single channel properties. In this respect the immunized rat end-plate is a good model for myasthenia gravis affected human end-plates.

Acetylcholine↗
PubMed1980

Interaction between nerve-related acetylcholine and bath applied agonists at the frog end-plate.

1. The interaction between acetylcholine (ACh) and carbachol (CCh) has been studied at the frog end-plate. The conditioning agonist, CCh, can cause desensitization (reduction of the ACh test response) and potentiation (increase of the test response). 2. Nerve-evoked end-plate currents (e.p.c.s), minature e.p.c.s and "slow" responses to ACh ionophoresis can all be potentiated by bath or ionophoretically applied CCh. 3. Since potentiation was found to be particularly visible at low temperatures, most experiments were performed at 5-8 degrees C. Potentiation results in an increase of both e.p.c. amplitude and e.p.c. decay time. Potentiated e.p.c.s teminate with a slow tail, the amplitude of which shows a high voltage sensitivity. Potentiation increases with CCh concentration (range studied 0-100 microM). It appears to persist throughout the application of CCh, even when desensitization is apparently the dominant phenomenon. 4. It is suggested that cross-potentiation of ACh by CCh results from the formation of intermediate non-conducting CCh-receptor complexes which have a high probability of being subsequently activated by ACh, yielding a conducting ACh-CCh-receptor complex. 5. Desensitization induced by fast bath application of CCh (or ACh) develops in two phases and can be fitted by the sum of two exponentials. Their time constants are in the second and the minute range, respectively. 6. The possibility that the slow phase is linked to the presence of agonist inside the cell is rejected.

Acetylcholine↗
PubMed1980

On the release of transmitter at normal, myasthenia gravis and myasthenic syndrome affected human end-plates.

1. Transmitter release has been studied at normal, myasthenia gravis (m.g.) and myasthenic syndrome (m.s.) affected human end-plates. At normal and diseased end-plates evoked transmitter release is Poisson for a mean quantal content, m less than ten. 2. The relation between log m and log [Ca]o, at normal and m.g. end-plates is linear, with a slope of 3.3-3.4. The value of m at m.g. end-plates is about five times larger than normal, below Ca 0.7 mM (Mg, 2mM). This difference in m is reduced at higher Ca levels. 3. The slope of the relation between log m.e.p.p. frequency and log [K]o is similar at normal and m.g. end-plates. Over its linear portion the relationship has a slope of approximately 6. 4. Fluctuations in the latency of evoked transmitter release were compared at normal and m.g. nerve terminals. At normal end-plates the probability of release reaches a peak about 0.3-0.4 msec after unitary e.p.p.s of the shortest latency and returns to zero about 1.0 msec after the peak. At m.g. end-plates the distribution of latencies shows less uniformity. 5. At m.s. end-plates m is approximately 5 in normal Ringer solution (2 mM-Ca, 1 mM-Mg). The relation between log m and log [Ca]o is linear, with a slope of 1.0-1.5. The K dependence of m.e.p.p. frequency appears reduced at m.s. end-plates. 6. Assuming a co-operative mechanism for transmitter release at normal human motor nerve terminals, the dissociation constant for the Ca complex is about 1.6X10(-3) M and the dissociation constant for the Mg complex is about 1.0X10(-3) M. 7. It is concluded that the presynaptic changes, at m.g. end-plates, are not the primary cause of the defect in nerve muscle transmission. At m.s. end-plates the presynaptic changes are sufficient to account for failure in transmission. Possible mechanisms for the abnormalities in transmitter release are considered.

Action Potentials↗
PubMed1979

End-plate currents and acetylcholine noise at normal and myasthenic human end-plates.

1. The amplitudes and time courses of miniature end-plate currents (m.e.p.c.s) have been compared at normal and myasthenic (MG) human end-plates studied under voltage clamp. The m.e.p.c. amplitude at MG end-plates is reduced to about one third normal; mean m.e.p.c. (normal) = 2.6 +/- 0.2 nA, mean m.e.p.c. (MG) = 1.0 +/- 0.1 nA. The decay time constant of m.e.p.c.s (tau m.e.p.c.) is very similar at normal and MG end-plates; tau m.e.p.c. (normal) = 1.70 +/- 0.1 msec, tau m.e.p.c. (MG) = 1.80 +/- 0.13 msec (Vm = - 80 mV. T = 23 degrees C). 2. The equilibrium potential of the end-plate current (e.p.c.) at normal and myasthenic human end-plates is close to 0 mV. 3. Decay time constants tau e.p.c. and tau m.e.p.c. increase exponentially with membrane hyperpolarization. The voltage sensitivity of the time constants was similar at normal and MG end-plates. 4. Both normal and myasthenic e.p.c.s are greatly prolonged in the presence of neostigmine (10(-6) g/ml.). At the same time the voltage sensitivity of tau e.p.c. is slightly reduced. 5. In response to steady ionophoretically applied ACh the mean membrane currents obtained at MG end-plates were smaller than the normal under similar conditions. 6. Analysis of end-plate current noise obtained during the steady application of acetylcholine (ACh) to voltage clamped normal and MG human end-plates showed that the amplitude of the elementary current event (gamma) and the average channel life-fime (tau noise) was similar at the two sites: tau noise (normal) - 1.54 +/- 0.04 msec, tau noise (MG) = 1.60 +/- 0.11 msec; gamma(normal) - 22.3 +/- 1.57 PS, gamma (MG) = 20.25 +/- 1.93 pS (Vm = - 80 mV, T = 23 degrees C). The voltage sensitivity of the channel life time, measured from end-plate current noise, was similar at normal and MG end-plates. 7. At normal human end-plates a packet of transmitter opens about 1500 channels whereas at MG end-plates a packet opens only about 600 channels. It is calculated that the size of the transmitter packets released from MG-terminals is at least as large as the packet of the ACh released from normal human nerve terminals.

Acetylcholine↗
PubMed1977

Analysis of atropine action at the frog neutromuscular junction.

1. Atropine action on the end-plate currents (e.p.c.s) has been analysed at the macroscopic and elementary levels. 2. The shortening effect of atropine on the e.p.c. and m.e.p.c. level can be fully explained by a reduction of the life time of the elementary current: this effect is markedly increased at more hyperpolarized membrane potentials and at higher concentrations of atropine. 3. It is therefore suggested that atropine binds to the open acetylcholine-receptor complex, leading to a state with a null conductance. According to this model, the forward rate constant of atropine binding could be calculated and was of the order of 10(7) M-1 S-1 AT -90 MV and 20-22 degrees C. 4. Although the conductance at the peak of the e.p.c. is reduced by atropine and becomes voltage sensitive, the elementary conductance is affected neither by voltage nor by atropine. 5. The exclusive binding of atropine to the activated ACh-receptor complex, as proposed above, does not appear to explain this phenomenon. Another binding occurring before the channel is open with a dissociation constant of 60 micrometer could account for this effect.

Animals↗
PubMed1976

Further investigations on the effect of denervation and pH on the conductance change at the neuromuscular junction of the frog.

Currents induced by acetylcholine application at the voltage-calmped frog end-plate, were measured over a large range of membrane potentials. Due to a non-linearity of the current-voltage curve, the directly-measured reversal potential may be quite different from the value classically determined by extrapolation (linear regression) of the measurements made at potentials below spike threshold. Denervation and changes of external pH were found to alter the shape of the current-voltage relation, but not the directly-measured reversal potential. These effects are tentatively explained on the basis of changes in the ratio: time-to-peak for [ACh] reaching the receptors/mean life-time of the open synaptic channels. Possible changes in cooperativity are also considered.

Acetylcholine↗
PubMed1973

Ionic properties of the neuromuscular junction of the frog: effects of denervation and pH.

1. The effects of denervation, reinnervation and pH on the ionic permeability changes mediated by junctional receptors have been studied in muscle fibres of the frog sartorius.2. The reversal potential of acetylcholine responses in denervated junctions was about 25 mV more negative than in normal junctions.3. The delay of the change in the ionic properties of junctional receptors was proportional to the nerve stump length: 10 and 14 days for lengths of 12 and 33 mm, respectively.4. When the motor nerve reinnervates the junction, the reversal potential of the acetylcholine responses comes back to the normal value before the neuromuscular transmission is restored.5. The Na/K conductance change decreases in high pH solutions. After denervation, the pH profile of this ratio is shifted to the acid values by about two pH units.6. These observations can be explained by assuming that the Na and K channels differ by the pK of their anionic groups and that the denervation induces an alteration of the sites that bear the charges.

Acetylcholine↗